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Effect of nitroglycerin and papaverine on coronary flow in man
Effect of nitroglycerin coronary flow in man
and pepaverine
on
Hendrick B. Barrier, M.D. George C. Kaiser, M.D. Vallee L. Willman, M.D. St. Louis. MO.
Nitroglycerin is widely utilized in the management of angina pectoris, but there is disagreement concerning its effect on coronary flow in man. Coronary flow measurement by nitrous oxide,’ 9ubidium coincidence counting,2-5 radioactive s6krypton,6and radioactive 133xenon7,8 has revealed an increase, decrease, or no change in coronary flow after nitroglycerin in patients with and without coronary artery disease. However, these techniques do not detect transient changes in blood flow. More recent use of methods that discriminate evanescent flow changes again do not give consistent results. A nonquantitative method9 indicates an increase in coronary flow after nitroglycerin while two quantitative studies indicate that there is no significant changelo or a decrease in coronary flow.” In this study the electromagnetic flowmeter has been used to measure flow in coronary bypass grafts in response to intra-arterial and intravenous nitroglycerin which is compared with papaverine. Method
Mean blood flow was measured in 28 saphenous vein coronary bypass grafts in 22 patients operated on for chronic angina pectoris. Studies were performed during hemodynamic stability 20 to 30 minutes after discontinuation of cardiopulmonary bypass. Transfusion with whole blood was continuous to replace concurrent loss. From
the Department
Supported by Grant Health Service. Received
for publication
of Surgery, No.
St. Louis
HL-06312 Oct.
from
University, the
United
St. Louis. States
Public
5, 19’73.
Reprint requests to: Hendrick B. Earner, gery, St. Louis University, 1325 S. Grand,
M.D., Department of SurSt. Louis, MO. 63104.
July, 1974, Vvl. 88, No. 1, pp. 13-17
Plow probes (Carolina Medical Electronics 400 Series) were laboratory calibrated in a gravityflow system using a canine arterial segment and canine blood with a hematocrit of 35 per cent and a temperature of 33 to 35” C. Timed collections of blood were made in the flow ranges found clinically and the probes were accurate to + 8 per cent. Arterial pressure was measured with a 16gauge radial artery cannula and a Statham P23Db strain gauge. Data were continuously recorded on a direct writing recorder (Brush, Mark 260). Nitroglycerin tablets were sterilized with ethylene oxide, diluted with physiologic saline to a concentration of 0.2 mg. per milliliter less than 10 minutes prior to use, and passed through a Millipore filter (Millipore Corporation, Swinnex-13, SXHA 013 OS 0.45~). Nitroglycerin (0.4 mg.) was given intravenously as a 2 ml. bolus and papaverine (30 mg.) was given as a 1 ml. bolus; intra-arterial nitroglycerin (0.1 mg.) and papaverine (15 mg.) were given into the bypass graft as a 0.5 ml. bolus over five seconds. Two patients received sublingual nitroglycerin (0.4 mg.) and three patients received physiologic saline 0.5 ml. intra-arterially. Mean arterial pressure was calculated by adding one-third of the difference between the systolic and diastolic pressure to the diastolic pressure. Peripheral resistance (millimeters of mercury per milliliter per minute) was calculated as the quotient of mean arterial pressure (millimeters of mercury) and mean flow (milliliters per minute). Data were calculated every 15 seconds for one minute, every 30 seconds for two minutes, and then at one minute intervals until return to control level or stabilization. American
Heart Journal
13
Bamer,
Kaiser,
and
Willman
7
0
2
4
6
MINUTES
Fig. 1. Mean control values f S.E.M. and mean per cent change from control f 1 S.E.M. are shown for 28 grafts studied with intravenous nitroglycerin in which graft flow = milliliten per minute, mean arterial pressure = MAP, coronary vascular resistance = resistance, and heart rate = HR.
% CHANGE NITROGLYCERIN
100
MAP 90f3
+25 O-c^u
:
-
z
0.1 mg IA
,
:
RESISTANCE 1.706+.214
Fig. 2. Same as Fig. 1 for 17 grafts studied with intra-arterial nitroglycerin.
Results
The data are in which mean mean per cent trol values are Intravenous flow at 15 (4 f
14
summarized in Figs. 1,2,4, and 5 control values f 1 S.E.M. and the change f 1 S.E.M. from the conshown for each time interval. nitroglycerin increases coronary 1.0 per cent, p
onds and then flow falls significantly below control to reach a nadir (23 + 3 per cent) at two minutes followed by a gradual return to control at five minutes (Fig. 1). The mean arterial pressure is unchanged at 15 seconds, has begun its decline at 30 seconds (8 -+ 1.1 per cent, p (0.0011, and reaches a low at 90 seconds before returning to control at six minutes. Coronary vascular resistance falls in the initial minute (p (0.001) but rises by two minutes (p (0.001) and remains elevated until six minutes. Heart rate is significantly elevated from 60 to 180 seconds. The response to sublingual nitroglycerin (0.4 mg.) in two of these patients was similar to that following intravenous administration, but there was no increase in coronary flow and the duration of diminished coronary fiow and arterial pressure was longer (8 to 10 minutes). Intra-arterial nitroglycerin (Fig. 2) achieves a peak coronary flow in 15 seconds (74 f 6 per cent) which returns to control by 90 seconds and then gradually drifts below control at five and six minutes (p (0.05). Although mean arterial pressure declines at five and six minutes, this change is not statistically significant nor is the increase in coronary vascular resistance. Heart rate is stable. Intra-arterial saline produced a distinct increase in coronary flow but of a much lesser magnitude than the nitroglycerin (Fig. 3). Papaverine intravenously (Fig. 4) produces a maximal coronary flow at 30 seconds (76 + 21 per cent) followed by an initial steep decline which levels out at three minutes 15 to 20 per cent above control (p < 0.02) and persists at this level. Mean arterial pressure falls maximally at 45 seconds and returns to control by three minutes and there is a 49 & 4 per cent decline in coronary vascular resistance during this interval. Heart rate is significantly elevated from 30 to 120 seconds (p (0.025). Intra-arterial papaverine Wig. 5) produces a maximal flow response at 45 seconds (215 f 23 per cent) with a return to control by five minutes. There is an associated fall in mean arterial pressure which is maximal at 60 seconds (17 * 2 per cent, p (0.001) and has returned to control by 150 seconds. The fall in coronary vascular resistance is correspondingly great (72 + 2 per cent). Heart rate is significantly elevated from 45 to 120 seconds.
July, 1974, Vol. 88, No, 1
Effect of nitroglycerin
and papaverine
on coronary
flow
IL 56 M LAD I
200 mm#ig 0 200 ml/min
M
Oseconds
t
t
Saline OSml IA Fig. 3. Mean arterial pressure (upper trace) tion of physiologic saline and nitroglycerin.
and coronary
NITROGLYCERIN O.lmg IA graft
flow are shown
in response
to intra-arterial
injec-
%
Discussion
CHANGE
These studies demonstrate an increase (maximal 4 per cent) in coronary bypass graft flow lasting 15 to 30 seconds followed by a decrease (maximal 23 per cent) in flow lasting five minutes as mean arterial pressure fell 24 per cent after intravenous nitroglycerin (0.4 mg.). These observations are similar to those in a comparable studylo in which a smaller dose of nitroglycerin (0.15 mg.) was used, and resulted in an increase in coronary flow in only one out of five patients and a smaller, nonsignificant (10 per cent) decrease as mean arterial pressure fell 27 per cent. These differences may be attributed to the smaller dose of nitroglycerin and the few observations. Our dosage was selected on the basis that it is a clinical dosage unit and the systemic pressure response to sublingual administration of this dose was comparable to the intravenous response in the two patients so studied. Our observations are consistent with those of Benchimol, Desser, and Gartlang in which inhaled amyl nitrate and sublingual nitroglycerin resulted in an increase in coronary flow that appears transient but is not quantitated or correlated with arterial pressure. Electromagnetic flowmeter studies in normal dogs reveal a pattern of response to intravenous nitroglycerin that is similar to that in man.12J3 The initial increase in coronary flow is greater
American
Heart
Journal
MINUTES
Fig. 4. Same papaverine.
as Fig. 1 for 14 grafts
studied
with
intravenous
(35 per centI and 67 per cent9 but persists for only 20 seconds and flow then falls below control for two minutes more. Ganz and Marcusll have measured coronary sinus flow by continuous thermodilution and found that intracoronary nitroglycerin increases coronary flow 27 to 147 per cent in normal man and 2 to 55 per cent in 14 out of 25 patients with coronary artery disease .ll Coronary sinus flow did not increase in six patients receiving intravenous nitroglycerin. Since our flow measurements were in diseased vessels having bypass grafts they may
15
Barner,
Kaiser,
and
Willman
% CHANGE 1
I
greater usage. However, its value is limited by lack of a sublingual dosage form. The value of oral papaverine in the management of angina pectoris cannot be ascertained from these studies. Summary
FLOW 65+6
OF
1
RESISTANCE 1.755k.196
MINUTES
Fig. 5. Same papaverine.
as Fig.
1 for grafts
studied
with
intra-arterial
be considered to fall into an intermediate group between the normal patients and those with occluded coronaries. Their observed flow responses to nitroglycerin are remarkably similar to ours with the exception that they did not observe the 20-second increase in flow after intravenous nitroglycerin. Our observations lend support to the concept that nitroglycerin relieves angina through its effect on the systemic circulation and not via an increase in coronary flo~.~Jl-‘~ Even though we observed a transient rise in coronary flow it is unlikely that this small increase would contribute to angina1 relief, and it may be absent in those with coronary disease” or dependent on intravenous administration.12J3 Furthermore, the myocardial distribution of the increased flow is unknown but it is unlikely that it is distributed to areas of need or ischemia.” The observations on papaverine have been reported because they offer some basis for comparison with nitroglycerin. It is apparent that papaverine in the dose used is a more effective coronary vasodilator and a less effective systemic vasodilator than is nitroglycerin. If clinical effectiveness is based in part on an increase in coronary flow then papaverine would warrant
16
Blood flow has been measured in 28 aortocoronary saphenous vein bypass grafts performed for chronic angina pectoris using the electromagnetic flowmeter. Nitroglycerin, 0.4 mg. intravenously or 0.1 mg. into the graft, and papaverine 30 mg. intravenously or 15 mg. into the graft, were studied. Intravenous nitroglycerin increased coronary flow a maximum of 4 per cent for 20 seconds followed by 23 per cent decline as mean arterial pressure fell 23 per cent. Intra-arterial nitroglycerin increased coronary flow 74 per cent in 15 seconds with return to control by 90 seconds. Intravenous papaverine elevated coronary flow 76 per cent at 30 seconds with stabilization of flow 15 to 20 per cent above control. Intra-arterial papaverine achieves a maximum flow of 215 per cent at 45 seconds with return to control at five minutes. Although nitroglycerin produces a small but significant rise in coronary flow it is doubtful whether this increase occurs with oral administration in the presence of coronary disease. Thus, the therapeutic effect of nitroglycerin lies in its systemic effects rather than in its coronary effect. REFERENCES 1.
2.
3.
4.
5.
Gorlin, R., Brachfeld, N., MacLeod, C., and Bopp, P.: Effect of nitroglycerin on the coronary circulation in patients with coronary artery disease or increased left ventricular work, Circulation 19: 705, 1959. Cohen, A., Gallagher, J. P., Luebs, E., Varga, Z., Yamanka, J., Zaleski, E. J., Bluemchen, G., and Bing, R. J.: The quantitative determination of coronary flow with a positron emitter (rubidium-841, Circulation 32: 636, 1965. Luebs, E. D., Cogen, A., Zaleski, E. J., and Bing, R. J.: Effect of nitroglycerin, intensain, isoptin, and papaverine on coronary blood flow in man. Measured by the coincidence-counting technique and rubidium, Am. J. Cardiol. 17: 535, 1966. Knoebel, S. B., McHenry, P. L., Roberts, D., and Stein, L.: Myocardial blood flow in man measured by the coincidence-counting system and a single bolus of s4rubidium chloride. Effect of nitroglycerin, Circulation 37: 932, 1969. Cowan, C., Duran, P. V. M., Corsini, G., Goldschlager, N., and Bing, R. J.: The effects of nitroglycerin on myocardial blood flow in man. Measured by coincidence-counting and bolus injections of rubidium, Am. J. Cardiol. 24: 154, 1969.
July, 1974, Vol. 88, No. 1
Effect of nitroglycerin
6.
7.
8.
9.
10
11
*I.
Parker, J. O., West, R. O., and DiGiorgi, S.: The effect of nitroglycerin on coronary blood flow and the hemodynamic response to exercise in coronary artery disease, Am. J. Cardiol. 27: 59, 1971. Bernstein, L., Friesinger, G. C., Lichtlin, P. R., and Ross, R. S.: The effect of nitroglycerin on the systemic and coronary circulation in man and dogs: myocardial blood flow measured with xenon, Circulation 33: 107, 1966. Carson, R. P., Wilson, W. S., Nemiroff, M. F., and Weber, W. J.: The effects of sublingual nitroglycerin on myocardial blood flow in patients with coronary artery disease or myocardial hypertrophy, AM. HEART J. 77: 579,1969. Benchimol, A., Desser, K. B., and Gartlan, J. L.: Effects of amyl nitrate on coronary arterial blood-flow velocity in man, Am. J. Cardiol. 30: 327, 1972. Greenfield, J. C., Jr., Rembert, J. C., Young, W. G., Oldham, H. N., Alexander, J. A., and Sabiston, D. C.: Studies of blood flow in aorta-to-coronary venous bypass grafts in man, J. Clin. Invest. 51: 2724, 1972. Ganz, W., and Marcus. H. S.: Failure of intracoronary
American
Heart Journal
12.
13.
14.
15.
16.
and papaverine
on cor0nar.y flow
nitroglycerin to alleviate pacing-induced angina, Circulation 46: 880, 1972. Vyden, F. K., Carvalho, M., Bosxormenyi. E., Lang, T., Bernstein, H., and Corday, E.: Effect of glyceryl trinitrate (nitroglycerin) on the systemic and coronary circulation of the doa. Am. J. Cardiol. 25: 53, 1970. Gillis, R. A., and Melville, K. I.: Effects of sublingually and intravenously administered nitroglycerin on the cardiovascular system of the dog, Am. J. Cardiol. 28: 38, 1971. Campion, B. C., Frye, R. L., and Zitnik, R. S.: Effects of nitroglycerin on capacitance vessels: a mechanism for reduction of left ventricular end-diastolic pressure, Mayo Clin. Proc. 46:573, 1970. Mason, D. T., and Braunwald, E.: The effects of nitroglycerin and amyl nitrate on arteriolar and venous tone in the human forearm, Circulation 32: 755, 1965. Williams. J. F.. Glick. G.. and Braunwald. E.: Studies on cardiac dimensions in intact unanesthetixed man. V. Effect of nitroglycerin, Circulation 32: 767, 1965.
17
and pepaverine
on
Hendrick B. Barrier, M.D. George C. Kaiser, M.D. Vallee L. Willman, M.D. St. Louis. MO.
Nitroglycerin is widely utilized in the management of angina pectoris, but there is disagreement concerning its effect on coronary flow in man. Coronary flow measurement by nitrous oxide,’ 9ubidium coincidence counting,2-5 radioactive s6krypton,6and radioactive 133xenon7,8 has revealed an increase, decrease, or no change in coronary flow after nitroglycerin in patients with and without coronary artery disease. However, these techniques do not detect transient changes in blood flow. More recent use of methods that discriminate evanescent flow changes again do not give consistent results. A nonquantitative method9 indicates an increase in coronary flow after nitroglycerin while two quantitative studies indicate that there is no significant changelo or a decrease in coronary flow.” In this study the electromagnetic flowmeter has been used to measure flow in coronary bypass grafts in response to intra-arterial and intravenous nitroglycerin which is compared with papaverine. Method
Mean blood flow was measured in 28 saphenous vein coronary bypass grafts in 22 patients operated on for chronic angina pectoris. Studies were performed during hemodynamic stability 20 to 30 minutes after discontinuation of cardiopulmonary bypass. Transfusion with whole blood was continuous to replace concurrent loss. From
the Department
Supported by Grant Health Service. Received
for publication
of Surgery, No.
St. Louis
HL-06312 Oct.
from
University, the
United
St. Louis. States
Public
5, 19’73.
Reprint requests to: Hendrick B. Earner, gery, St. Louis University, 1325 S. Grand,
M.D., Department of SurSt. Louis, MO. 63104.
July, 1974, Vvl. 88, No. 1, pp. 13-17
Plow probes (Carolina Medical Electronics 400 Series) were laboratory calibrated in a gravityflow system using a canine arterial segment and canine blood with a hematocrit of 35 per cent and a temperature of 33 to 35” C. Timed collections of blood were made in the flow ranges found clinically and the probes were accurate to + 8 per cent. Arterial pressure was measured with a 16gauge radial artery cannula and a Statham P23Db strain gauge. Data were continuously recorded on a direct writing recorder (Brush, Mark 260). Nitroglycerin tablets were sterilized with ethylene oxide, diluted with physiologic saline to a concentration of 0.2 mg. per milliliter less than 10 minutes prior to use, and passed through a Millipore filter (Millipore Corporation, Swinnex-13, SXHA 013 OS 0.45~). Nitroglycerin (0.4 mg.) was given intravenously as a 2 ml. bolus and papaverine (30 mg.) was given as a 1 ml. bolus; intra-arterial nitroglycerin (0.1 mg.) and papaverine (15 mg.) were given into the bypass graft as a 0.5 ml. bolus over five seconds. Two patients received sublingual nitroglycerin (0.4 mg.) and three patients received physiologic saline 0.5 ml. intra-arterially. Mean arterial pressure was calculated by adding one-third of the difference between the systolic and diastolic pressure to the diastolic pressure. Peripheral resistance (millimeters of mercury per milliliter per minute) was calculated as the quotient of mean arterial pressure (millimeters of mercury) and mean flow (milliliters per minute). Data were calculated every 15 seconds for one minute, every 30 seconds for two minutes, and then at one minute intervals until return to control level or stabilization. American
Heart Journal
13
Bamer,
Kaiser,
and
Willman
7
0
2
4
6
MINUTES
Fig. 1. Mean control values f S.E.M. and mean per cent change from control f 1 S.E.M. are shown for 28 grafts studied with intravenous nitroglycerin in which graft flow = milliliten per minute, mean arterial pressure = MAP, coronary vascular resistance = resistance, and heart rate = HR.
% CHANGE NITROGLYCERIN
100
MAP 90f3
+25 O-c^u
:
-
z
0.1 mg IA
,
:
RESISTANCE 1.706+.214
Fig. 2. Same as Fig. 1 for 17 grafts studied with intra-arterial nitroglycerin.
Results
The data are in which mean mean per cent trol values are Intravenous flow at 15 (4 f
14
summarized in Figs. 1,2,4, and 5 control values f 1 S.E.M. and the change f 1 S.E.M. from the conshown for each time interval. nitroglycerin increases coronary 1.0 per cent, p
onds and then flow falls significantly below control to reach a nadir (23 + 3 per cent) at two minutes followed by a gradual return to control at five minutes (Fig. 1). The mean arterial pressure is unchanged at 15 seconds, has begun its decline at 30 seconds (8 -+ 1.1 per cent, p (0.0011, and reaches a low at 90 seconds before returning to control at six minutes. Coronary vascular resistance falls in the initial minute (p (0.001) but rises by two minutes (p (0.001) and remains elevated until six minutes. Heart rate is significantly elevated from 60 to 180 seconds. The response to sublingual nitroglycerin (0.4 mg.) in two of these patients was similar to that following intravenous administration, but there was no increase in coronary flow and the duration of diminished coronary fiow and arterial pressure was longer (8 to 10 minutes). Intra-arterial nitroglycerin (Fig. 2) achieves a peak coronary flow in 15 seconds (74 f 6 per cent) which returns to control by 90 seconds and then gradually drifts below control at five and six minutes (p (0.05). Although mean arterial pressure declines at five and six minutes, this change is not statistically significant nor is the increase in coronary vascular resistance. Heart rate is stable. Intra-arterial saline produced a distinct increase in coronary flow but of a much lesser magnitude than the nitroglycerin (Fig. 3). Papaverine intravenously (Fig. 4) produces a maximal coronary flow at 30 seconds (76 + 21 per cent) followed by an initial steep decline which levels out at three minutes 15 to 20 per cent above control (p < 0.02) and persists at this level. Mean arterial pressure falls maximally at 45 seconds and returns to control by three minutes and there is a 49 & 4 per cent decline in coronary vascular resistance during this interval. Heart rate is significantly elevated from 30 to 120 seconds (p (0.025). Intra-arterial papaverine Wig. 5) produces a maximal flow response at 45 seconds (215 f 23 per cent) with a return to control by five minutes. There is an associated fall in mean arterial pressure which is maximal at 60 seconds (17 * 2 per cent, p (0.001) and has returned to control by 150 seconds. The fall in coronary vascular resistance is correspondingly great (72 + 2 per cent). Heart rate is significantly elevated from 45 to 120 seconds.
July, 1974, Vol. 88, No, 1
Effect of nitroglycerin
and papaverine
on coronary
flow
IL 56 M LAD I
200 mm#ig 0 200 ml/min
M
Oseconds
t
t
Saline OSml IA Fig. 3. Mean arterial pressure (upper trace) tion of physiologic saline and nitroglycerin.
and coronary
NITROGLYCERIN O.lmg IA graft
flow are shown
in response
to intra-arterial
injec-
%
Discussion
CHANGE
These studies demonstrate an increase (maximal 4 per cent) in coronary bypass graft flow lasting 15 to 30 seconds followed by a decrease (maximal 23 per cent) in flow lasting five minutes as mean arterial pressure fell 24 per cent after intravenous nitroglycerin (0.4 mg.). These observations are similar to those in a comparable studylo in which a smaller dose of nitroglycerin (0.15 mg.) was used, and resulted in an increase in coronary flow in only one out of five patients and a smaller, nonsignificant (10 per cent) decrease as mean arterial pressure fell 27 per cent. These differences may be attributed to the smaller dose of nitroglycerin and the few observations. Our dosage was selected on the basis that it is a clinical dosage unit and the systemic pressure response to sublingual administration of this dose was comparable to the intravenous response in the two patients so studied. Our observations are consistent with those of Benchimol, Desser, and Gartlang in which inhaled amyl nitrate and sublingual nitroglycerin resulted in an increase in coronary flow that appears transient but is not quantitated or correlated with arterial pressure. Electromagnetic flowmeter studies in normal dogs reveal a pattern of response to intravenous nitroglycerin that is similar to that in man.12J3 The initial increase in coronary flow is greater
American
Heart
Journal
MINUTES
Fig. 4. Same papaverine.
as Fig. 1 for 14 grafts
studied
with
intravenous
(35 per centI and 67 per cent9 but persists for only 20 seconds and flow then falls below control for two minutes more. Ganz and Marcusll have measured coronary sinus flow by continuous thermodilution and found that intracoronary nitroglycerin increases coronary flow 27 to 147 per cent in normal man and 2 to 55 per cent in 14 out of 25 patients with coronary artery disease .ll Coronary sinus flow did not increase in six patients receiving intravenous nitroglycerin. Since our flow measurements were in diseased vessels having bypass grafts they may
15
Barner,
Kaiser,
and
Willman
% CHANGE 1
I
greater usage. However, its value is limited by lack of a sublingual dosage form. The value of oral papaverine in the management of angina pectoris cannot be ascertained from these studies. Summary
FLOW 65+6
OF
1
RESISTANCE 1.755k.196
MINUTES
Fig. 5. Same papaverine.
as Fig.
1 for grafts
studied
with
intra-arterial
be considered to fall into an intermediate group between the normal patients and those with occluded coronaries. Their observed flow responses to nitroglycerin are remarkably similar to ours with the exception that they did not observe the 20-second increase in flow after intravenous nitroglycerin. Our observations lend support to the concept that nitroglycerin relieves angina through its effect on the systemic circulation and not via an increase in coronary flo~.~Jl-‘~ Even though we observed a transient rise in coronary flow it is unlikely that this small increase would contribute to angina1 relief, and it may be absent in those with coronary disease” or dependent on intravenous administration.12J3 Furthermore, the myocardial distribution of the increased flow is unknown but it is unlikely that it is distributed to areas of need or ischemia.” The observations on papaverine have been reported because they offer some basis for comparison with nitroglycerin. It is apparent that papaverine in the dose used is a more effective coronary vasodilator and a less effective systemic vasodilator than is nitroglycerin. If clinical effectiveness is based in part on an increase in coronary flow then papaverine would warrant
16
Blood flow has been measured in 28 aortocoronary saphenous vein bypass grafts performed for chronic angina pectoris using the electromagnetic flowmeter. Nitroglycerin, 0.4 mg. intravenously or 0.1 mg. into the graft, and papaverine 30 mg. intravenously or 15 mg. into the graft, were studied. Intravenous nitroglycerin increased coronary flow a maximum of 4 per cent for 20 seconds followed by 23 per cent decline as mean arterial pressure fell 23 per cent. Intra-arterial nitroglycerin increased coronary flow 74 per cent in 15 seconds with return to control by 90 seconds. Intravenous papaverine elevated coronary flow 76 per cent at 30 seconds with stabilization of flow 15 to 20 per cent above control. Intra-arterial papaverine achieves a maximum flow of 215 per cent at 45 seconds with return to control at five minutes. Although nitroglycerin produces a small but significant rise in coronary flow it is doubtful whether this increase occurs with oral administration in the presence of coronary disease. Thus, the therapeutic effect of nitroglycerin lies in its systemic effects rather than in its coronary effect. REFERENCES 1.
2.
3.
4.
5.
Gorlin, R., Brachfeld, N., MacLeod, C., and Bopp, P.: Effect of nitroglycerin on the coronary circulation in patients with coronary artery disease or increased left ventricular work, Circulation 19: 705, 1959. Cohen, A., Gallagher, J. P., Luebs, E., Varga, Z., Yamanka, J., Zaleski, E. J., Bluemchen, G., and Bing, R. J.: The quantitative determination of coronary flow with a positron emitter (rubidium-841, Circulation 32: 636, 1965. Luebs, E. D., Cogen, A., Zaleski, E. J., and Bing, R. J.: Effect of nitroglycerin, intensain, isoptin, and papaverine on coronary blood flow in man. Measured by the coincidence-counting technique and rubidium, Am. J. Cardiol. 17: 535, 1966. Knoebel, S. B., McHenry, P. L., Roberts, D., and Stein, L.: Myocardial blood flow in man measured by the coincidence-counting system and a single bolus of s4rubidium chloride. Effect of nitroglycerin, Circulation 37: 932, 1969. Cowan, C., Duran, P. V. M., Corsini, G., Goldschlager, N., and Bing, R. J.: The effects of nitroglycerin on myocardial blood flow in man. Measured by coincidence-counting and bolus injections of rubidium, Am. J. Cardiol. 24: 154, 1969.
July, 1974, Vol. 88, No. 1
Effect of nitroglycerin
6.
7.
8.
9.
10
11
*I.
Parker, J. O., West, R. O., and DiGiorgi, S.: The effect of nitroglycerin on coronary blood flow and the hemodynamic response to exercise in coronary artery disease, Am. J. Cardiol. 27: 59, 1971. Bernstein, L., Friesinger, G. C., Lichtlin, P. R., and Ross, R. S.: The effect of nitroglycerin on the systemic and coronary circulation in man and dogs: myocardial blood flow measured with xenon, Circulation 33: 107, 1966. Carson, R. P., Wilson, W. S., Nemiroff, M. F., and Weber, W. J.: The effects of sublingual nitroglycerin on myocardial blood flow in patients with coronary artery disease or myocardial hypertrophy, AM. HEART J. 77: 579,1969. Benchimol, A., Desser, K. B., and Gartlan, J. L.: Effects of amyl nitrate on coronary arterial blood-flow velocity in man, Am. J. Cardiol. 30: 327, 1972. Greenfield, J. C., Jr., Rembert, J. C., Young, W. G., Oldham, H. N., Alexander, J. A., and Sabiston, D. C.: Studies of blood flow in aorta-to-coronary venous bypass grafts in man, J. Clin. Invest. 51: 2724, 1972. Ganz, W., and Marcus. H. S.: Failure of intracoronary
American
Heart Journal
12.
13.
14.
15.
16.
and papaverine
on cor0nar.y flow
nitroglycerin to alleviate pacing-induced angina, Circulation 46: 880, 1972. Vyden, F. K., Carvalho, M., Bosxormenyi. E., Lang, T., Bernstein, H., and Corday, E.: Effect of glyceryl trinitrate (nitroglycerin) on the systemic and coronary circulation of the doa. Am. J. Cardiol. 25: 53, 1970. Gillis, R. A., and Melville, K. I.: Effects of sublingually and intravenously administered nitroglycerin on the cardiovascular system of the dog, Am. J. Cardiol. 28: 38, 1971. Campion, B. C., Frye, R. L., and Zitnik, R. S.: Effects of nitroglycerin on capacitance vessels: a mechanism for reduction of left ventricular end-diastolic pressure, Mayo Clin. Proc. 46:573, 1970. Mason, D. T., and Braunwald, E.: The effects of nitroglycerin and amyl nitrate on arteriolar and venous tone in the human forearm, Circulation 32: 755, 1965. Williams. J. F.. Glick. G.. and Braunwald. E.: Studies on cardiac dimensions in intact unanesthetixed man. V. Effect of nitroglycerin, Circulation 32: 767, 1965.
17