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Hemodynamic effects of hydralazine in patients with isolated right ventricular failure
ASSESSMENT OF PRAZOSIN ALPHA RECEPTOR BLOCKADE NI!l'H PA-LANINE: XUTE, BUBPCUTB AND LATE HFXODYNANIC EVALUATION DURING SUSTAINED BENEFICIAL VASODILATOR TBBF+ APY IN CONGESTIVE HEART FAILURE Mark K. Evenson, BS; Najam A. Awan, MD, FACT; Kathleen E. Needham. BS: and Dean T. Mason. ND, FRCC. Universitv of California, Davis. The mechanism of transient subacute hemodynamic blunting of prazosin (PZ) effects in therapy of chronic congestive
MAXIMAL IMPROVEMENT IN VENTRICULAR PERFORMANCE DURING REST AND EXERCISE IN CHRONIC SEVERE CARDIAC FAILURE BY COMBINED INOTROPIC AND VASODILATOR THERAPY COMPARED TO EITHER MODALITY ALONE. Stephen P. Rosenfeld, M.D., FACC, M. Sheila Carnev. R.N.. Alan D. Waanoner, RDMS. Lawrence R. Poliner, M.D:; FACC; Miguel A. -&ino&?s, M.D., FACC, Craig M. Pratt, M.D., FACC, Richard R. Miller, M.D., FACC, Baylor College of Medicine, Houston, Texas.
heart failure the efficacy
Acutely, combined positive inotropic and vasodilator (Vas) therapy is superior to either individually in LV failure (F); however, the comparative effects chronically and at both rest (Rst) and exercise (Ex) are unknown. We compared digitalis (Dig) (serum level 1.3k.l ng/ml) plus maximal Vas [prazosin (n=4) or hydralazine + nitrate (n= 14)] and diuretic (DT) vs Dig+DT vs Vas+DT vs DT alone in 18 patients with extreme LVF [mean LV ejection fraction (EF) 16+7 (SD) % (all ~30%). (nine ischemic)l bv Rst and ix ;adi&&lide E+, treadmill-(T) tolerance.isec), phone and 48 hr ECG. T-Ex Rst-EF Ex-EF PEP/LVET PVC/hr --EDD ----362+40 6.5+.8 16+2 73+27 20+3 .59+.06 DT 336+61 6.6T.8 Dig 21+2t 21+3 .507.03** 88532 82+24 395z50 6.55.8 .57x.04 Vas 19?3* 23z5 Dig+Vas 23+3** 26+3tY 409270 6.5+.7 111+67 .53+.05 EDD=end-diastolic dimension (cm). *zp<.O5 vsDT; I=~<.02 vs Dig. Left atria1 vs DT; **=p<.O5 vs DT and Vas; 'i'=p<.O5 size was similar (p=ns) in each group. With Dig, Rst heart rate + and Rst + Ex BP 4 (pc.02) vs DT and Vas. Dig+Vas had lower (pc.02) PVC severity score vs Vas although PVC/ hr were similar (p=ns). Thus, in extreme LVF neither Dig nor Vas separately increase Kx-EF vs DT alone. Dig+Vas combined f Rst and Ex-EF vs DT, 4 Rst-EF vs Vas and 4 ExEF vs Dig (both px.05). These data provide objective rationale for the chronic "se of combined inotropic and vasodilator therapy in extreme LV dysfunction.
(CliF) is uncertain. of PZ alpha receptor
Therefore we evaluated (AR) blockade by phento-
lamine (PT, 1.3 mg/min) acutely (Day 11, subacutely (Day 4) and chronically (Day 30) during continuous unaltered PZ (5 mg qid) therapy. Measuremants: mean blood pressure (&BP), nmUig; left ventricular fisling pressure (LVPP), nnnHg; cardiac index (Cl) L/min/M . Drug vs control (C):
l=p:o.o5,
l*=p
+=p
NBP LWPCI NBP LVFP CI MBP LVFP CI C 85 22 2.1 83 25 2.3 83 23 2.0 PT 72+ 16* 2.4* 75+ 23* 2.6+ 79. 19+ 2.5' PZ 71+ 17+ 2.6+ 82 23 2.5 74+ 17** 2.8+ PZ+PT 7O*O 16+ 2.5+ 78*O 21*O 2.7+O 78* 19" 2.6++ Accordingly, while the beneficial vasodilator effects of PT on cardiac function are blunted by salutary acute PZ responses on Day 1, during transient subacute PZ "tachyphylaxis" (Day 4) phentolamine responses are unaltered by PZ. Further with continuous 30 day oral PZ therapy of CKF, the spontaneous return of beneficial PZ effects causes restoration of post-P2 phentolamine block on Day 30. Thus the mechanism of transient PZ “tachyphylaxis” is temporarily modified PZ-AR relation while the alpha receptor itself remains responsive to vasodilation. Importantly, transient subacute blunting of PZ hemodynm ic effects by modified PZ-AR interaction does not effect successful long term therapy of CHF with prasosin.
HEMODYNAMIC EFFECTS OF HYDRALAZINE IN PATIENTS WITH ISOLATED RIGHT VENTRICULAR FAILURE Franklin Handel, MD; Robert H. Peter, MD, FACC; Lewis J. Rubin, MD, Duke University Medical Center, Durham, N.C. Fifteen patients with isolated right ventricular failure secondary to pulmonary hypertension were evaluated for response to oral hydralazine(H). Three had idiopathic pulmonary hypertension, three closed ASDs, two closed VSDs, three COPD, two chronic pulmonary emboli, and two pulmonary fibrosis. All patients underwent right heart catheterization; none had LV dysfunction. Mean systemic pressure(MSP), mean pulmonary artery pressure(MPP), right atria1 pressure@&, right ventricular end diastolic pressure(RVEDP), pulmonary capillary wedge pressure(PCWF), cardiac index(CI), arteriovenous 02 difference(AV02), heart rate(HR), total pulmonary resistance(TPR), and pulmonary arteriolar resistance(PAR) were measured for all patients at baseline(C). Rest studies (H) were then repeated after eight doses of 50 mg H orally q6h.
R Mean
I~.5sp Ibfw Iti IRVEDF IPcwpI cI IAvo2 99 62 15 17 9 2.2 8.0 +29
f23
?7
57 11 +S.D. 87 223 f21 ?6 H * x* P p = *<.;3; **<.01; test.
?5
+3
+.6
22.3
HR 87 ?15
TF'R PAR 19 12 t14
t6
3.2 6.2 95 13 7 11 8 *4 t5 +3 kl.l f2.0 k13 ill *** *** *xx * *** *** NS ***<.OOl by Student's two-tailed t
The above data suggests that oral hydralazine significantly increases cardiac output, lowers right ventricular end diastolic pressure, and lowers pulmonary vascular resistance in patients with right ventricular failure secondary to pulmonary hypertension.
390
February 1981
The American Journal of CARDIOLOGY
INHIBITION OF NITROGLYCERIN EFFECT IN HUMANS BY SUPPRESSION OF PROSTAGLANDIN E James Van Dusen, D.O.; Stephen J. Fischl, M.D., FACC; Overlook Hospital, Summit, New Jersey 10 healthy volunteers were studied supine using a mercuryin-rubber strain gauge plethysomograph and indwelling venous pressure cannula in the forearm. Volume-pressure characteristics of the forearm veins were determined using 15 second automatic cuff occlusions of the limb. Percent change of forearm volume (XAV) and change of venous compliance (C) were measured at rest and following 0.1 mg. sublingual nitroglycerin (NTG). Indomethacin (I) 150 mg. per day was administered to each volunteer for one week and the measurements were repeated. The expected increments in limb volume and C during control cuff occlusions were 28% and 26% higher,respectively, after NTG. After I therapy and cuff occlusion, increments in limb volume and C were 25% and 39X, respectively, lower than control. While on I, mean increments in limb volume and C did not change significantly following NTG. 15 second occlusion @ 40 mmHg %A in volume C(%A in volume/mmHg) Control 1;; ; *;; (PC.05) 1;;; ; *ii; (pi.05) NTG I-Control .24 t :04 .014 f :004 I & NTG .22 f .04 .013 t .013 Therefore, augmentation of volume and compliance of the peripheral vasculature by NTG is inhibited by prior administration of I. presumably by suppression of prostaglandin E synthesis. This supports the concept that prostaglandins may be important mediators for the action of NTG in humans. Perhaps, patients receiving nitrates should be observed for this possible drug interaction with prostaglandin-inhibiting drugs.
Volume 47
MAXIMAL IMPROVEMENT IN VENTRICULAR PERFORMANCE DURING REST AND EXERCISE IN CHRONIC SEVERE CARDIAC FAILURE BY COMBINED INOTROPIC AND VASODILATOR THERAPY COMPARED TO EITHER MODALITY ALONE. Stephen P. Rosenfeld, M.D., FACC, M. Sheila Carnev. R.N.. Alan D. Waanoner, RDMS. Lawrence R. Poliner, M.D:; FACC; Miguel A. -&ino&?s, M.D., FACC, Craig M. Pratt, M.D., FACC, Richard R. Miller, M.D., FACC, Baylor College of Medicine, Houston, Texas.
heart failure the efficacy
Acutely, combined positive inotropic and vasodilator (Vas) therapy is superior to either individually in LV failure (F); however, the comparative effects chronically and at both rest (Rst) and exercise (Ex) are unknown. We compared digitalis (Dig) (serum level 1.3k.l ng/ml) plus maximal Vas [prazosin (n=4) or hydralazine + nitrate (n= 14)] and diuretic (DT) vs Dig+DT vs Vas+DT vs DT alone in 18 patients with extreme LVF [mean LV ejection fraction (EF) 16+7 (SD) % (all ~30%). (nine ischemic)l bv Rst and ix ;adi&&lide E+, treadmill-(T) tolerance.isec), phone and 48 hr ECG. T-Ex Rst-EF Ex-EF PEP/LVET PVC/hr --EDD ----362+40 6.5+.8 16+2 73+27 20+3 .59+.06 DT 336+61 6.6T.8 Dig 21+2t 21+3 .507.03** 88532 82+24 395z50 6.55.8 .57x.04 Vas 19?3* 23z5 Dig+Vas 23+3** 26+3tY 409270 6.5+.7 111+67 .53+.05 EDD=end-diastolic dimension (cm). *zp<.O5 vsDT; I=~<.02 vs Dig. Left atria1 vs DT; **=p<.O5 vs DT and Vas; 'i'=p<.O5 size was similar (p=ns) in each group. With Dig, Rst heart rate + and Rst + Ex BP 4 (pc.02) vs DT and Vas. Dig+Vas had lower (pc.02) PVC severity score vs Vas although PVC/ hr were similar (p=ns). Thus, in extreme LVF neither Dig nor Vas separately increase Kx-EF vs DT alone. Dig+Vas combined f Rst and Ex-EF vs DT, 4 Rst-EF vs Vas and 4 ExEF vs Dig (both px.05). These data provide objective rationale for the chronic "se of combined inotropic and vasodilator therapy in extreme LV dysfunction.
(CliF) is uncertain. of PZ alpha receptor
Therefore we evaluated (AR) blockade by phento-
lamine (PT, 1.3 mg/min) acutely (Day 11, subacutely (Day 4) and chronically (Day 30) during continuous unaltered PZ (5 mg qid) therapy. Measuremants: mean blood pressure (&BP), nmUig; left ventricular fisling pressure (LVPP), nnnHg; cardiac index (Cl) L/min/M . Drug vs control (C):
l=p:o.o5,
l*=p
+=p
NBP LWPCI NBP LVFP CI MBP LVFP CI C 85 22 2.1 83 25 2.3 83 23 2.0 PT 72+ 16* 2.4* 75+ 23* 2.6+ 79. 19+ 2.5' PZ 71+ 17+ 2.6+ 82 23 2.5 74+ 17** 2.8+ PZ+PT 7O*O 16+ 2.5+ 78*O 21*O 2.7+O 78* 19" 2.6++ Accordingly, while the beneficial vasodilator effects of PT on cardiac function are blunted by salutary acute PZ responses on Day 1, during transient subacute PZ "tachyphylaxis" (Day 4) phentolamine responses are unaltered by PZ. Further with continuous 30 day oral PZ therapy of CKF, the spontaneous return of beneficial PZ effects causes restoration of post-P2 phentolamine block on Day 30. Thus the mechanism of transient PZ “tachyphylaxis” is temporarily modified PZ-AR relation while the alpha receptor itself remains responsive to vasodilation. Importantly, transient subacute blunting of PZ hemodynm ic effects by modified PZ-AR interaction does not effect successful long term therapy of CHF with prasosin.
HEMODYNAMIC EFFECTS OF HYDRALAZINE IN PATIENTS WITH ISOLATED RIGHT VENTRICULAR FAILURE Franklin Handel, MD; Robert H. Peter, MD, FACC; Lewis J. Rubin, MD, Duke University Medical Center, Durham, N.C. Fifteen patients with isolated right ventricular failure secondary to pulmonary hypertension were evaluated for response to oral hydralazine(H). Three had idiopathic pulmonary hypertension, three closed ASDs, two closed VSDs, three COPD, two chronic pulmonary emboli, and two pulmonary fibrosis. All patients underwent right heart catheterization; none had LV dysfunction. Mean systemic pressure(MSP), mean pulmonary artery pressure(MPP), right atria1 pressure@&, right ventricular end diastolic pressure(RVEDP), pulmonary capillary wedge pressure(PCWF), cardiac index(CI), arteriovenous 02 difference(AV02), heart rate(HR), total pulmonary resistance(TPR), and pulmonary arteriolar resistance(PAR) were measured for all patients at baseline(C). Rest studies (H) were then repeated after eight doses of 50 mg H orally q6h.
R Mean
I~.5sp Ibfw Iti IRVEDF IPcwpI cI IAvo2 99 62 15 17 9 2.2 8.0 +29
f23
?7
57 11 +S.D. 87 223 f21 ?6 H * x* P p = *<.;3; **<.01; test.
?5
+3
+.6
22.3
HR 87 ?15
TF'R PAR 19 12 t14
t6
3.2 6.2 95 13 7 11 8 *4 t5 +3 kl.l f2.0 k13 ill *** *** *xx * *** *** NS ***<.OOl by Student's two-tailed t
The above data suggests that oral hydralazine significantly increases cardiac output, lowers right ventricular end diastolic pressure, and lowers pulmonary vascular resistance in patients with right ventricular failure secondary to pulmonary hypertension.
390
February 1981
The American Journal of CARDIOLOGY
INHIBITION OF NITROGLYCERIN EFFECT IN HUMANS BY SUPPRESSION OF PROSTAGLANDIN E James Van Dusen, D.O.; Stephen J. Fischl, M.D., FACC; Overlook Hospital, Summit, New Jersey 10 healthy volunteers were studied supine using a mercuryin-rubber strain gauge plethysomograph and indwelling venous pressure cannula in the forearm. Volume-pressure characteristics of the forearm veins were determined using 15 second automatic cuff occlusions of the limb. Percent change of forearm volume (XAV) and change of venous compliance (C) were measured at rest and following 0.1 mg. sublingual nitroglycerin (NTG). Indomethacin (I) 150 mg. per day was administered to each volunteer for one week and the measurements were repeated. The expected increments in limb volume and C during control cuff occlusions were 28% and 26% higher,respectively, after NTG. After I therapy and cuff occlusion, increments in limb volume and C were 25% and 39X, respectively, lower than control. While on I, mean increments in limb volume and C did not change significantly following NTG. 15 second occlusion @ 40 mmHg %A in volume C(%A in volume/mmHg) Control 1;; ; *;; (PC.05) 1;;; ; *ii; (pi.05) NTG I-Control .24 t :04 .014 f :004 I & NTG .22 f .04 .013 t .013 Therefore, augmentation of volume and compliance of the peripheral vasculature by NTG is inhibited by prior administration of I. presumably by suppression of prostaglandin E synthesis. This supports the concept that prostaglandins may be important mediators for the action of NTG in humans. Perhaps, patients receiving nitrates should be observed for this possible drug interaction with prostaglandin-inhibiting drugs.
Volume 47