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Surface pH changes during and after myocardial ischemia in primates
Surface pH changes during and after myocardial ischemia in primates Surface pH was measured in primate myocardium before and during periods of coronary ligation varying from 15 minutes to 4 hours. pH fell (7.43 to 6.95) after ligation, and release of the ligature produced a prompt return to preligation pH values. Return to normal pH occurred even in infarcted muscle and was thought to represent return of blood flow in spite of muscle infarction.
J. Judson McNamara, M.D., John R. Soeter, M.D., Glenn T. Suehiro, B.S., Richard J. Anema, and Gregory T. Smith, B.S., Honolulu, Hawaii
The present study began as an attempt to use surface pH determinations to map the area of ischemia following coronary ligation in primates. The electrode proved too large to provide precise definition of the infarct boundaries on the small monkey hearts. However, a profound drop in pH was recorded when the electrode was placed in the center of the infarcted area. The present study had two phases. In first group of animals, pH was measured before and after ligatures were placed in the center of the infarct and in a neutral area away from the area of ischemia. This area was produced by ligation of the left anterior descending coronary artery (LAD). Following completion of this phase of the study, a second group of animals was studied in which the ligature was released 30 minutes to 3 hours after placement. Surface pH was again recorded in the infarcted and neutral areas before and after ligature replacement and then again after ligature release.
(I mg. per kilogram) and intramuscular and intravenous sodium Pentothal (12.5 mg. per dose) as needed. Ventilation was maintained by endotracheal mechanical ventilation. A catheter was placed in the femoral artery to monitor adequacy of ventilation and blood pH. Via a left thoracotomy, the pericardium was opened and a snare was placed around the LAD just distal to the first diagonal branch. Surface pH was determined at two sites,
Materials and methods
Eleven Macaca monkeys weighing 2.5 to 4 kilograms were anesthetized with Sernylan From the Department of Surgery. University of Hawaii School of Medicine and Cardiovascular Research Laboratory, Queen's Medical Center, Honolulu, Hawaii. Supported by U. S. Public Health Grant HEW NIL 1 ROi HL14571~1 SGYB. Received for publication June 18, 1973.
Fig. 1. Diagram of monkey heart surface as seen through left thoracotomy. Ligature is below the first small diagonal branch. pH determinations were taken at Points A and B as indicated.
191
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The Journal 01 Thoracic and Cardiovascular Surgery
McNamara et al.
p.(O 001
I A (1) X 7.46
p.c.0.001
1-
s
.17
p<0.05
I
(1) X 7.48
B
B
'it
6.92 s
\
I
I A (2)
s
.19
.19
(2) 'it
iI
7.31 s
.18
Fig. 2. Mean surface pH values (X) before (1) and after (2) ligation at Points A and B in 15 ani'mals. pH before ligation was 7.46 at Point A and 7.48 at Point B. After ligation, pH was 6.92 at Point A and 7.31 at Point B. s, Standard deviation.
Point A in the center of the ischemic area of myocardium and Point B on the posterior heart in an area of nonischemic myocardium (Fig. 1). pH measurements were taken immediately before ligation in 15 animals and immediately before ligature release. In 6 animals, pH was determined before and after ligature placement and, in addition, 15 minutes after ligature release. The duration of ligation in each animal was varied (15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, and 4 hours). These animals were allowed to live for a week before being put to death. Serial sections were then taken of the heart for histologic examination. Results
Blood pH remained stable for the duration of the study with a preligation mean value of 7.33 (± 0.5) and a postligation mean of 7.35 (± 0.7). In both groups of animals, pH was the same in Area A and Area B before ligation (Figs. 2 and 3). Following ligation, pH dropped significantly (p < 0.001) within 15 to 30 minutes in Area A. A small but significant drop (p < 0.05) was noted in Area B, less than that noted in Area A (p < 0.001). pH level in Area A did not drop further in ligations that lasted longer than 30 minutes. There was no correlation between the duration of ligation and the degree of recovery toward normal pH in Area A following ligature release. The observed recovery in the 6 animals studied
after ligature release (from pH 6.95 to 7.31) was significant in Area A (p < 0.01) but not Area B (p > 0.05) (Fig. 2). The pH following ligature release did riot differ significantly from preligation pH in either Area A or B. Histologic sections of myocardium were taken from animals subjected to ligation for 15 minutes to 4 hours and then allowed to survive for a week. These sections showed clear evidence of an established infarct in all animals in which the ligation period lasted over 30 minutes. However, animals sustaining a longer period of ligation appeared, subsequently, to have a larger infarction (Fig. 4). Discussion
The surface pH of the anterior left ventricular myocardium fell rapidly in the present study following ligation of the LAD. The drop in pH occurred within 15 minutes following ligation. This is consistent with the findings of Couch and Middleton." The major decline in pH which they observed in ischemic rabbit hearts occurred in less than an hour after the onset of ischemia. pH fell slightly on posterior wall myocardium although the change was not significant. It is conceivable that the significant ventricular dysfunction occurring with LAD ligation may have resulted in a general decline in myocardial perfusion and, concomitantly, myocardial pH. Following release of the ligature, the pH
Volume 67
Surface pH changes in myocardial ischemia
Number 2
193
Februory, 1974
•
--"P.:...<=-O.:....O-=l:.----------..
p,>O.05
I I __
o.t.O.05
I
8
. 13
I
A (2}
I 6.:, .16
Fig. 3. Mean surface pH values from 15 minutes to 5 hours. pH ligation (2) pH values were 6.95 (3) were 7.31 at Point A and 7.36
A (3)
x
7.31
s
.16
B £1) 7.43
s
. 12
J
I
r-. 1---'-, p>0.05
. ---1..
B (2)
B (3)
7.27 s .09
it 7.36 s .16
x
in 6 animals that had coronary ligation for periods ranging before ligation (1) was 7.43 at both Points A and B. During at Point A and 7.27 at Point B. The postligation pH values at Point B.
Fig. 4. Cross section of monkey heart subjected to 5 hours of ischemia. The animal was put to death 10 days later. A transmural infarct with scar formation is clearly evident in the anterior ventricle .
returned rapidly to near preligation levels in all animals, regardless of the duration of ligation. Our studies and others by Herdson and co-workers- have shown that infarction occurs after 30 minutes - to an hour of ischemia. Furthermore, in all animals that survived for a week after sustaining over an hour of coronary ligation, the area of Point A was always infarcted. This means that pH returns to normal in an area of infarcted nonviable muscle. Considering the rapidity of the rise of pH toward normal and the fact that it occurs in an area where muscle is
infarcted, it appears that pH reflects only a return of blood flow into the infarcted area. Our data on surface pH change following coronary ligation are similar to those reported by Cohn and co-workers ." We also observed that myocardial surface pH was higher than blood pH, although this difference was not statistically significant in our study . The present data present evidence that blood flow does return following revascularization of an occluded coronary artery in a monkey and raise the possibility that signifi-
1 94
McNamara et at.
cant thrombosis may not occur acutely in the vascular bed during the period of ischemia. REFERENCES Gazzaniga, A. B., Byrd, C. L., and Gross, R. E.: The Use of Skeletal Muscle Surface Hydrogen Ion Concentration to Monitor Peripheral Perfusion: Experimental and Clinical Results, Surg. Forum 22: 147, 1971. 2 Couch, N. P., and Middleton, M. K.: Effect of Storage Temperature on the Electromagnetic Surface Hydrogen Ion Activity of Ischemic Liver and Heart, Surgery 64: 1099, 1968.
The Journol of Thoracic and Cardiovoscular Surgery
3 Bermann, I. R., Lemieux, M. D., and Aaby, G. V.: Responses of Skeletal Muscle pH to Injury: A New Technique for Determination of Tissue Viability, Surgery 67: 507, 1970. 4 Herdson, P. B., Sommers, H. M., and Jennings, R. B.: A Comparative Study of the Fine Structure of Normal and Ischemic Dog Myocardium With Special Reference to Early Changes Following Temporary Occlusion of a Coronary Artery, Am. J. Patho!. 46: 367, 1965. 5 Cohn, L. H., Denvaert, F., and Collins, J. J.: The Detection of Ischemic Myocardium by Surface pH Measurements, Circulation 46: 15, 1972 (Supp!. 11).
J. Judson McNamara, M.D., John R. Soeter, M.D., Glenn T. Suehiro, B.S., Richard J. Anema, and Gregory T. Smith, B.S., Honolulu, Hawaii
The present study began as an attempt to use surface pH determinations to map the area of ischemia following coronary ligation in primates. The electrode proved too large to provide precise definition of the infarct boundaries on the small monkey hearts. However, a profound drop in pH was recorded when the electrode was placed in the center of the infarcted area. The present study had two phases. In first group of animals, pH was measured before and after ligatures were placed in the center of the infarct and in a neutral area away from the area of ischemia. This area was produced by ligation of the left anterior descending coronary artery (LAD). Following completion of this phase of the study, a second group of animals was studied in which the ligature was released 30 minutes to 3 hours after placement. Surface pH was again recorded in the infarcted and neutral areas before and after ligature replacement and then again after ligature release.
(I mg. per kilogram) and intramuscular and intravenous sodium Pentothal (12.5 mg. per dose) as needed. Ventilation was maintained by endotracheal mechanical ventilation. A catheter was placed in the femoral artery to monitor adequacy of ventilation and blood pH. Via a left thoracotomy, the pericardium was opened and a snare was placed around the LAD just distal to the first diagonal branch. Surface pH was determined at two sites,
Materials and methods
Eleven Macaca monkeys weighing 2.5 to 4 kilograms were anesthetized with Sernylan From the Department of Surgery. University of Hawaii School of Medicine and Cardiovascular Research Laboratory, Queen's Medical Center, Honolulu, Hawaii. Supported by U. S. Public Health Grant HEW NIL 1 ROi HL14571~1 SGYB. Received for publication June 18, 1973.
Fig. 1. Diagram of monkey heart surface as seen through left thoracotomy. Ligature is below the first small diagonal branch. pH determinations were taken at Points A and B as indicated.
191
1 92
The Journal 01 Thoracic and Cardiovascular Surgery
McNamara et al.
p.(O 001
I A (1) X 7.46
p.c.0.001
1-
s
.17
p<0.05
I
(1) X 7.48
B
B
'it
6.92 s
\
I
I A (2)
s
.19
.19
(2) 'it
iI
7.31 s
.18
Fig. 2. Mean surface pH values (X) before (1) and after (2) ligation at Points A and B in 15 ani'mals. pH before ligation was 7.46 at Point A and 7.48 at Point B. After ligation, pH was 6.92 at Point A and 7.31 at Point B. s, Standard deviation.
Point A in the center of the ischemic area of myocardium and Point B on the posterior heart in an area of nonischemic myocardium (Fig. 1). pH measurements were taken immediately before ligation in 15 animals and immediately before ligature release. In 6 animals, pH was determined before and after ligature placement and, in addition, 15 minutes after ligature release. The duration of ligation in each animal was varied (15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, and 4 hours). These animals were allowed to live for a week before being put to death. Serial sections were then taken of the heart for histologic examination. Results
Blood pH remained stable for the duration of the study with a preligation mean value of 7.33 (± 0.5) and a postligation mean of 7.35 (± 0.7). In both groups of animals, pH was the same in Area A and Area B before ligation (Figs. 2 and 3). Following ligation, pH dropped significantly (p < 0.001) within 15 to 30 minutes in Area A. A small but significant drop (p < 0.05) was noted in Area B, less than that noted in Area A (p < 0.001). pH level in Area A did not drop further in ligations that lasted longer than 30 minutes. There was no correlation between the duration of ligation and the degree of recovery toward normal pH in Area A following ligature release. The observed recovery in the 6 animals studied
after ligature release (from pH 6.95 to 7.31) was significant in Area A (p < 0.01) but not Area B (p > 0.05) (Fig. 2). The pH following ligature release did riot differ significantly from preligation pH in either Area A or B. Histologic sections of myocardium were taken from animals subjected to ligation for 15 minutes to 4 hours and then allowed to survive for a week. These sections showed clear evidence of an established infarct in all animals in which the ligation period lasted over 30 minutes. However, animals sustaining a longer period of ligation appeared, subsequently, to have a larger infarction (Fig. 4). Discussion
The surface pH of the anterior left ventricular myocardium fell rapidly in the present study following ligation of the LAD. The drop in pH occurred within 15 minutes following ligation. This is consistent with the findings of Couch and Middleton." The major decline in pH which they observed in ischemic rabbit hearts occurred in less than an hour after the onset of ischemia. pH fell slightly on posterior wall myocardium although the change was not significant. It is conceivable that the significant ventricular dysfunction occurring with LAD ligation may have resulted in a general decline in myocardial perfusion and, concomitantly, myocardial pH. Following release of the ligature, the pH
Volume 67
Surface pH changes in myocardial ischemia
Number 2
193
Februory, 1974
•
--"P.:...<=-O.:....O-=l:.----------..
p,>O.05
I I __
o.t.O.05
I
8
. 13
I
A (2}
I 6.:, .16
Fig. 3. Mean surface pH values from 15 minutes to 5 hours. pH ligation (2) pH values were 6.95 (3) were 7.31 at Point A and 7.36
A (3)
x
7.31
s
.16
B £1) 7.43
s
. 12
J
I
r-. 1---'-, p>0.05
. ---1..
B (2)
B (3)
7.27 s .09
it 7.36 s .16
x
in 6 animals that had coronary ligation for periods ranging before ligation (1) was 7.43 at both Points A and B. During at Point A and 7.27 at Point B. The postligation pH values at Point B.
Fig. 4. Cross section of monkey heart subjected to 5 hours of ischemia. The animal was put to death 10 days later. A transmural infarct with scar formation is clearly evident in the anterior ventricle .
returned rapidly to near preligation levels in all animals, regardless of the duration of ligation. Our studies and others by Herdson and co-workers- have shown that infarction occurs after 30 minutes - to an hour of ischemia. Furthermore, in all animals that survived for a week after sustaining over an hour of coronary ligation, the area of Point A was always infarcted. This means that pH returns to normal in an area of infarcted nonviable muscle. Considering the rapidity of the rise of pH toward normal and the fact that it occurs in an area where muscle is
infarcted, it appears that pH reflects only a return of blood flow into the infarcted area. Our data on surface pH change following coronary ligation are similar to those reported by Cohn and co-workers ." We also observed that myocardial surface pH was higher than blood pH, although this difference was not statistically significant in our study . The present data present evidence that blood flow does return following revascularization of an occluded coronary artery in a monkey and raise the possibility that signifi-
1 94
McNamara et at.
cant thrombosis may not occur acutely in the vascular bed during the period of ischemia. REFERENCES Gazzaniga, A. B., Byrd, C. L., and Gross, R. E.: The Use of Skeletal Muscle Surface Hydrogen Ion Concentration to Monitor Peripheral Perfusion: Experimental and Clinical Results, Surg. Forum 22: 147, 1971. 2 Couch, N. P., and Middleton, M. K.: Effect of Storage Temperature on the Electromagnetic Surface Hydrogen Ion Activity of Ischemic Liver and Heart, Surgery 64: 1099, 1968.
The Journol of Thoracic and Cardiovoscular Surgery
3 Bermann, I. R., Lemieux, M. D., and Aaby, G. V.: Responses of Skeletal Muscle pH to Injury: A New Technique for Determination of Tissue Viability, Surgery 67: 507, 1970. 4 Herdson, P. B., Sommers, H. M., and Jennings, R. B.: A Comparative Study of the Fine Structure of Normal and Ischemic Dog Myocardium With Special Reference to Early Changes Following Temporary Occlusion of a Coronary Artery, Am. J. Patho!. 46: 367, 1965. 5 Cohn, L. H., Denvaert, F., and Collins, J. J.: The Detection of Ischemic Myocardium by Surface pH Measurements, Circulation 46: 15, 1972 (Supp!. 11).