Protection of ischemic myocardium in conscious dogs with Nifedipine

1
ABSTRACTS PROTECTION OF ISCHEMIC MYOCARDIUM IN CONSCIOUS DOGS WITH NIFEDIPINE Philip Henry, MD; Rafael Shuchleib, MD; Edward Weiss, MD; Edward Hoffman, PhD; Robert Roberts, MD; Burton E. Sobel, MD, FACC, Washington University, St. Louis, Missouri To determine whether the coronary dilator and negative inotropic effects of Nifedipine (N), a potent Co*-antagonist, have a beneficial effect on the energy balance of ischemic myocardium, conscious dogs subjected to acute coranory occlusion were treated with N (4O&kg/min i.v.) or placebo (P), beginning 4 hour after onset of ischemia until sacrifice of the animal 24 hr later. Microspheres labeled with one of the three tracers were in’ected sequentially into the left otrium: 1) immediately before ( 85 2) immediately after (14’Ce), Sr); and 3) 24 hr after (5’Cr) onset of treatment. After sacrifice, multiple biopsies were obtained from non-ischemic ond ischemic myocardium and local flows at the times of microsphere injections calculated on the basis of radio- activity of the appropriate isotope. Local ischemic injury in the same biopsies was estimated by measuring myocardial creatine kinase (CK) activity. Pretreatment flows in N dogs (n=7) and P dogs (n=8) did not differ significantly, averaging 144, 2&Z, and 88% ml/lOOg/min in central ischemic, marginal, and non- ischemic zones. Flows immediately after onset of treatment with N in the corresponding zones increased to 36k7, 64f9, and 198 f25, but flows were unchanged with P. At 24 hr, flows in the 3 zones were 39*5, 72ti, and 162*14 with N, and 1223, 34i6, and 83* with P. CK activities in corresponding biopsies over- aged 789, 2080, and 2460 ofter N, and 208, 542, and 2540 lU/g fresh weight after P. These results indicate that N produces sustained increases in coronary flow accompanied by preservation of myocordiol CK activity indicative of protection. LEFT VETTRICULAR DIASTOLIC COMPLIA.WE IN AORTIC STENOSIS FOLLOWYC SWXSSFUL VALVE REPLACl%ENT Otto Hess, MD; Hans P. Krayenbuehl, MD; Norbert H. Coebel, MD; 8ke Senning, MD, University of Zurich, Zurich, Switzerland Left ventricular (LV) high-fidelity pressure measurements and quantitative cineangiography were carried out in 15 patients (pts) with aortic stenosis (AS) before and 13.5 months following valve replacement by a tilting disc pros- thesis. Eighteen pts without LV disease served as controls (C). LV diastolic compliance was assessed by: (1) total observed compliance (TCIC),i.e. angiographic stroke volume (V) related to LV diastolic pressure (I')change (~V,/AP) normalized for end-systolic volume and (2) LV passive elas tic modulus (stiffness index) determined as the slope (a) ofAPjAV per m2 related to mean LV diastolic pressure. In AS pre-op TOC amounted to 0.177 and was significantly (P< 0.001) decreased as compared to TOC in C (0.422). Postope- ratively TOC increased to 0.388 (P~0.01) and was not dif- ferent from TOC in C. The stiffness index (a) was greater in A? pre-op (0.0243) than in C (0.0014) and decreased to -0.0068 following surgery. At the preoperative study the pts (n=lO) with a TOC below the lower limit of normality had a significantly lower mean normalized systolic ejec- tion rate than those (n=5) with a T,X within normal limits Between these two subgroups there was however no diffe- rence in LV muscle mass or wall thickness. In conclusions, successful aortic valve replacement leads to a significant increase of preoperatively decreased LV diastolic compliance. The reduction of compliance prior to surgery appears to be related to depressed LV contrac- tile function rather than to hypertrophy per se. SUPERIOR MESENTERIC ARTERIAL BED RESPONSE TO DOPAMINE IN EXPERIMENTAL CARDIOGENIC SHOCK IN DOGS. Leroy Hirsch, Ph.D., Gerald Glick, M.D., F.A.C.C., Cardiovascular In- stitute, Michael Reese Hospital, Chicago, 111. During myocardial infarction complicated by shock, the mesenteric bed undergoes profound vasoconstriction. Dopa- mine has been suggested as a therapeutic agent in shock because of its ability to dilate the renal and mesenteric beds. Dogs in which electromagnetic bloodflow transducers had been implanted on the superior mesenteric artery, common hepatic artery, and portal vein were subjected to direct infusion of dopamine (2.5 ug/kg/min) into the superior mesenteric artery. In control dogs, dopamine in- creased superior mesenteric arterial blood flow (SMAQ) mope than 100%. Systemic intravenous administration, 10 w/k&in, increased SMAQ 59%. Embolization of the left circumflex coronary artery with 0.2 ml of mercury produced a circumscribed myocardial infarction which, over a period of several hours, led to cardiogenic shock and profound vasoconstriction in the superior mesenteric bed. During the period of shock, direct arterial infusion of dopamine produced either extremely small amounts of vasodilation or?no vasodilation at all. That the bed was capable of responding to vasodilator influences was shown by a 60% increase in SMAQ when isoproterenol was infused directly into the artery. Furthermore, when the alpha receptor blocking agent phenoxybenzamine was injected directly into the artery, the vasodilator response to dopamine was restored, suggesting that the dopaminergic receptors, in the mesenteric bed at least, may be related functionally, or stearically to alpha receptors. Thus, during cardiogenic shock, the mesenteric bed becomes un- responsive to the dilating action of dopamine, but res- ponsiveness can be restored by alpha receptor blockade. ECHOGRAPHIC ISOVOLUMIC CONTRACTION PERIOD IN THE EVALUATION OF LEFT VENTRICULAR MYOCARDIAL DISEASE. Stephen Hirschfeld,M.D., Richard Meyer, M.D.,Joon Korfhagen, U.T., Samuel Kaplan, M.D., F.A.C.C., Univ. Cinti., Dept. of Pediatrics, Childrens Hospital, Cinti., Ohio. Echocardiography was used to measure the isovolumic con- traction period (IVC) of the left ventricle (LV) in order to assess alterations of cardiac performance in children with LV myocardhl disease (LVMD). The echographic IVC was defined as the interval between coaptotion of the anterior and posterior mitral valve leaflets (MC) and aortic cusp opening (Ao). The intervols from the Q wave of the electrocardiogram (ECG) to Ao and the Q wove of the ECG to MC were determined and the IVC was measured as IVC=QAo-QMc. Forty-two normal children and 14 children with LVMD were evaluated. In normal children the IVC shortened with decreasing age and increasing heart rate. The mean IVC for age < 3 years = 22 + 9 msec, while for age > 3 years IVC = 33 + 7 msecr For heart rate >130 beats/minute IVC= 19 + 5 msec, while heart rate 70-130 IVC = 33 + 6 msec. In patients with LVMD the IVC was markedly prolonged. For age < 3 years and heort rote >130, IVC = 49 + 12 msec, while above age 3 and heart rate 70-130, the IVC was 62 + 21 msec. The measurements were reproducible and permitted serial evaluation of patients with LVMD and their response to therapy. Chonges were signi- ficant at 60.01 when compored to normals. Echocardiography may be used to determine IVC, which was useful as on additional non-invasive measure of LV contractility. 142 January 1976 The American Journal of CARDIOLOGY Volume 37

Transcript of Protection of ischemic myocardium in conscious dogs with Nifedipine

Page 1: Protection of ischemic myocardium in conscious dogs with Nifedipine

ABSTRACTS

PROTECTION OF ISCHEMIC MYOCARDIUM IN CONSCIOUS

DOGS WITH NIFEDIPINE

Philip Henry, MD; Rafael Shuchleib, MD; Edward Weiss, MD;

Edward Hoffman, PhD; Robert Roberts, MD; Burton E. Sobel, MD,

FACC, Washington University, St. Louis, Missouri

To determine whether the coronary dilator and negative inotropic

effects of Nifedipine (N), a potent Co*-antagonist, have a

beneficial effect on the energy balance of ischemic myocardium,

conscious dogs subjected to acute coranory occlusion were treated

with N (4O&kg/min i.v.) or placebo (P), beginning 4 hour

after onset of ischemia until sacrifice of the animal 24 hr later.

Microspheres labeled with one of the three tracers were in’ected

sequentially into the left otrium: 1) immediately before ( 85

2) immediately after (14’Ce),

Sr);

and 3) 24 hr after (5’Cr) onset of

treatment. After sacrifice, multiple biopsies were obtained from

non-ischemic ond ischemic myocardium and local flows at the

times of microsphere injections calculated on the basis of radio-

activity of the appropriate isotope. Local ischemic injury in the

same biopsies was estimated by measuring myocardial creatine

kinase (CK) activity. Pretreatment flows in N dogs (n=7) and P

dogs (n=8) did not differ significantly, averaging 144, 2&Z,

and 88% ml/lOOg/min in central ischemic, marginal, and non-

ischemic zones. Flows immediately after onset of treatment with

N in the corresponding zones increased to 36k7, 64f9, and 198

f25, but flows were unchanged with P. At 24 hr, flows in the 3

zones were 39*5, 72ti, and 162*14 with N, and 1223, 34i6,

and 83* with P. CK activities in corresponding biopsies over-

aged 789, 2080, and 2460 ofter N, and 208, 542, and 2540

lU/g fresh weight after P. These results indicate that N produces

sustained increases in coronary flow accompanied by preservation

of myocordiol CK activity indicative of protection.

LEFT VETTRICULAR DIASTOLIC COMPLIA.WE IN AORTIC STENOSIS FOLLOWYC SWXSSFUL VALVE REPLACl%ENT Otto Hess, MD; Hans P. Krayenbuehl, MD; Norbert H. Coebel, MD; 8ke Senning, MD, University of Zurich, Zurich, Switzerland

Left ventricular (LV) high-fidelity pressure measurements and quantitative cineangiography were carried out in 15 patients (pts) with aortic stenosis (AS) before and 13.5

months following valve replacement by a tilting disc pros- thesis. Eighteen pts without LV disease served as controls (C). LV diastolic compliance was assessed by: (1) total observed compliance (TCIC), i.e. angiographic stroke volume (V) related to LV diastolic pressure (I') change (~V,/AP) normalized for end-systolic volume and (2) LV passive elas tic modulus (stiffness index) determined as the slope (a) ofAPjAV per m2 related to mean LV diastolic pressure. In AS pre-op TOC amounted to 0.177 and was significantly (P< 0.001) decreased as compared to TOC in C (0.422). Postope- ratively TOC increased to 0.388 (P~0.01) and was not dif- ferent from TOC in C. The stiffness index (a) was greater

in A? pre-op (0.0243) than in C (0.0014) and decreased to

-0.0068 following surgery. At the preoperative study the pts (n=lO) with a TOC below the lower limit of normality had a significantly lower mean normalized systolic ejec- tion rate than those (n=5) with a T,X within normal limits Between these two subgroups there was however no diffe- rence in LV muscle mass or wall thickness. In conclusions, successful aortic valve replacement leads to a significant increase of preoperatively decreased LV diastolic compliance. The reduction of compliance prior to surgery appears to be related to depressed LV contrac- tile function rather than to hypertrophy per se.

SUPERIOR MESENTERIC ARTERIAL BED RESPONSE TO DOPAMINE IN EXPERIMENTAL CARDIOGENIC SHOCK IN DOGS. Leroy Hirsch, Ph.D., Gerald Glick, M.D., F.A.C.C., Cardiovascular In- stitute, Michael Reese Hospital, Chicago, 111.

During myocardial infarction complicated by shock, the mesenteric bed undergoes profound vasoconstriction. Dopa- mine has been suggested as a therapeutic agent in shock because of its ability to dilate the renal and mesenteric beds. Dogs in which electromagnetic bloodflow transducers had been implanted on the superior mesenteric artery, common hepatic artery, and portal vein were subjected to direct infusion of dopamine (2.5 ug/kg/min) into the superior mesenteric artery. In control dogs, dopamine in- creased superior mesenteric arterial blood flow (SMAQ) mope than 100%. Systemic intravenous administration, 10 w/k&in, increased SMAQ 59%. Embolization of the left circumflex coronary artery with 0.2 ml of mercury produced a circumscribed myocardial infarction which, over a period of several hours, led to cardiogenic shock and profound vasoconstriction in the superior mesenteric bed. During the period of shock, direct arterial infusion of dopamine produced either extremely small amounts of vasodilation or? no vasodilation at all. That the bed was capable of responding to vasodilator influences was shown by a 60% increase in SMAQ when isoproterenol was infused directly into the artery. Furthermore, when the alpha receptor blocking agent phenoxybenzamine was injected directly into the artery, the vasodilator response to dopamine was restored, suggesting that the dopaminergic receptors, in the mesenteric bed at least, may be related functionally, or stearically to alpha receptors. Thus, during cardiogenic shock, the mesenteric bed becomes un- responsive to the dilating action of dopamine, but res- ponsiveness can be restored by alpha receptor blockade.

ECHOGRAPHIC ISOVOLUMIC CONTRACTION PERIOD IN THE

EVALUATION OF LEFT VENTRICULAR MYOCARDIAL DISEASE.

Stephen Hirschfeld,M.D., Richard Meyer, M.D.,Joon Korfhagen,

U.T., Samuel Kaplan, M.D., F.A.C.C., Univ. Cinti., Dept. of

Pediatrics, Childrens Hospital, Cinti., Ohio.

Echocardiography was used to measure the isovolumic con-

traction period (IVC) of the left ventricle (LV) in order to assess

alterations of cardiac performance in children with LV myocardhl

disease (LVMD). The echographic IVC was defined as the interval

between coaptotion of the anterior and posterior mitral valve

leaflets (MC) and aortic cusp opening (Ao). The intervols from

the Q wave of the electrocardiogram (ECG) to Ao and the Q

wove of the ECG to MC were determined and the IVC was

measured as IVC=QAo-QMc. Forty-two normal children and 14

children with LVMD were evaluated. In normal children the IVC

shortened with decreasing age and increasing heart rate. The

mean IVC for age < 3 years = 22 + 9 msec, while for age > 3 years

IVC = 33 + 7 msecr For heart rate >130 beats/minute IVC= 19 +

5 msec, while heart rate 70-130 IVC = 33 + 6 msec. In patients

with LVMD the IVC was markedly prolonged. For age < 3 years

and heort rote >130, IVC = 49 + 12 msec, while above age 3 and

heart rate 70-130, the IVC was 62 + 21 msec. The measurements

were reproducible and permitted serial evaluation of patients

with LVMD and their response to therapy. Chonges were signi-

ficant at 60.01 when compored to normals. Echocardiography

may be used to determine IVC, which was useful as on additional

non-invasive measure of LV contractility.

142 January 1976 The American Journal of CARDIOLOGY Volume 37