SUMMARY Sodium pentobarbital (PB), 30 mg/kg, iv, was administered to 30 conscious dogs instrumented for measurement of cardiac output and regional blood flow distribution, left ventricular (LV) diameter, LV pressure, dP/dt, and dD/dt, i.e., velocity of myocardial fiber shortening. Ventilation was controlled during anesthesia to maintain arterial blood gases at control values for conscious dogs. The anesthetic produced an initial transient, peripheral vasodilation but the steady state effects 15-30 minutes later were characterized by slight reductions in mesenteric flow and cardiac output and increases in mesenteric and systemic resistances, whereas iliac and renal resistances were not significantly different from control. When heart rate rose, PB increased end-systolic diameter and decreased coronary resistance, LV end-diastolic diameter, dP/dt/P (42%), and shortening velocity (36%). When heart rate was controlled, PB still increased end-systolic diameter and decreased shortening velocity and dP/dt/P, as occurred during spontaneous rhythm, but end-diastolic diameter rose instead of falling and coronary resistance did not change. After recovery from bilateral cervical section of both carotid sinus and aortic nerves, PB failed to elicit tachycardia. Thus, PB affects systemic and regional hemodynamics only slightly, but depresses the myocardium markedly. The tachycardia associated with PB anesthesia in intact, trained dogs appears not to be only vagolytic, as previously thought, but is predominantly mediated through the arterial baroreceptor reflex.SODIUM PENTOBARBITAL remains one of the most widely used anesthetics for experimental cardiovascular studies. However, the effects of the anesthetic agent are generally disregarded in the interpretation of experimental data from studies in which PB is employed. This is due in part to the fact that the effects of this anesthetic are not completely known. In addition, results from previous studies, which indicated that the anesthetic has little effect on cardiac output and arterial pressure, 1 " 3 have previously been used as justification for disregarding its effects. The primary goal of this study was to provide a comprehensive picture of the effects of sodium pentobarbital (PB) on left ventricular (LV) function, coronary dynamics, distribution of regional blood flow, and regional vascular resistance. A secondary goal was to examine the mechanism for the PB-induced tachycardia, which is currently thought to be due to a vagolytic action. ultrasonic flow transducer was implanted around the left circumflex coronary artery, stimulator electrodes were sutured to the left atrium, a miniature pressure transducer (Konigsberg P22) was implanted through a stab wound in the apex of the left ventricle, and ultrasonic dimension transducers were implanted on opposing anterior and posterior endocardial surfaces of the left ventricle (14 dogs). In three of these 14 dogs and in six additional dogs, an electromagnetic flow transducer (Zepeda) was implanted around the ascending aorta. Thr...

A B S T R A C T The effects of coronary artery reperfusion at 1 and 3 h after occlusion on infarct size (IS) in the conscious dog were compared with a second group of dogs that were not reperfused (24 h occlusion). Infarct size was calculated from creatine kinase (CK) appearing in blood samples (ISJ) the serial blood CK curve was changed significantly by reperfusion. In dogs with a 24-h occlusion, CK rose gradually to a peak at 11.4±0.5 h. In dogs reperfused at 3 h, CK rose sharply at 3 h and reached a peak at 6.8±0.5 h, significantly earlier (P < 0.01) than occurred in dogs reperfused at 1 h, i.e., when the peak occurred at 4.2±0.4 h. The rapid appearance of CK in blood after reperfusion at 1 and 3 h suggested a washout phenomena. Thus, reperfusion alters the shape ofthe serial blood CK curve and results in a different linear relationship between calculated and measured infarct size, resulting in greater recovery of CK in blood per unit of infarcted myocardium.Dr. Vatner is an Established Investigator for the American Heart Association.

SUMMARY The effects of aging and smooth muscle activation on the elastic stiffness of the aortic wall were assessed in nine unanesthetized adult sheep, seven newborn (<1 week) lambs, and five near term fetal lambs in utero, previously instrumented with pressure gauges and ultrasonic dimension crystals for measurements of internal pressure and external diameter in the proximal third of the descending thoracic aorta. Angiotensin and nitroglycerin were administered as intravenous (iv) boluses to increase or decrease pressure and diameter. The midwall stress (u)-radius data were fitted to an exponential curve (r > 0.95) for each animal. The curves obtained in this way were similar to those obtained by inflating and deflating an implanted hydraulic occluder. Incremental elastic modulus (Einc) was derived as a linear function of stress. Compared at similar a levels, Eiac was significantly (P < 0.05) lower in the adults than in either the newborn or the fetuses. For example, at a -3.30 x 10* dynes/cm 1 , Ei«, was 1.41 ± 0.10 x 10* dynes/cm 1 in the adults, compared with 2.41 ± 0.35 in the lambs and 2.31 ± 0.15 in the fetuses. However, when Eim was calculated at the higher stress value corresponding to baseline mean arterial pressure, {a -6.90 ± 0.59 x 10* dynes/cm* in the adult, 3.36 ± 0.27 in the newborn, 3.62 ± 0.56 in the fetus), E&*. was only slightly higher in the adults (3.67 ± 0.50 x 10' dynes/ cm 1 ) than in the newborns (2.42 ± 0.38) or the fetuses (2.58 ± 0.58). a-Adrenergic activation of aortic smooth muscle, induced by methoxamine infusion, shifted pressure-diameter and stress-radius relationships toward higher pressure or stress for any given radius in the adult, whereas no alteration was observed in unanesthetized fetal or newborn lambs or in adults anesthetized with pentobarbitaL Thus the aortic elastic modulus at any given wall stress is lower in the unanesthetized adult sheep than in the newborn or the fetus. However, the responsiveness of aortic smooth muscle to a-adrenergic stimulation increases with age. Ore Res 44: 1979

A B S T R A C T The effects of methoxamine and nitroglycerin on measurements of large vessel (left circumflex) coronary dimensions were examined in eight conscious dogs using an ultrasonic dimension gauge, and total coronary resistance was calculated from measurements of arterial pressure and coronary blood flow. Methoxamine (50 ,ug/kg per min), after transiently increasing left circumflex coronary dimensions, induced sustained reductions in left circumflex diameter (9±2%) and external (18±4%) and internal (27±5%) cross-sectional areas, at a time when mean arterial pressure rose by 65±+5%, left ventricular dPIdt had decreased only slightly, and heart rate and mean coronary blood flow remained at control levels. Calculated large vessel and total coronary resistances rose similarly, i.e., by 108±29 and 92±14%, respectively. Methoxamine reduced coronary arterial wall stiffness from control at comparable stress levels, although at any common radius, wall stiffness was augmented substantially.Nitroglycerin (25 ,g/kg) induced an initial decrease in coronary dimensions along with the fall in arterial pressure. However, left circumflex coronary dimensions then rose, reaching a maximum 5 min later at a time when left circumflex coronary blood flow was reduced and heart rate and left ventricular dPIdt were at control levels. At this time, significantly different effects were observed on large vessel coronary resistance, which fell by 18±2%, and on total coronary resistance, which rose by 11±4%. Thus, in the conscious dog, large coronary vessels not only react passively to changes in aortic pressure but also undergo substantial Dr.

To determine if oxygen free radical scavengers administered before coronary artery reperfusion can limit reperfusion arrhythmias, increase the return of regional function in ischemic myocardium, and reduce tissue necrosis at 1 week after 90-minute coronary artery occlusion and reperfusion, conscious dogs were treated with superoxide dismutase (SOD) and catalase before and for 1 hour after coronary artery reperfusion. Another group was treated with recombinant SOD (rSOD) because the commercially available SOD and catalase contained endotoxin. The conscious dogs were studied 3-4 weeks after implanting left ventricular pressure gauges, ultrasonic wall thickness gauges in the posterior left ventricular wall, left atrial catheters, and arterial catheters, Doppler flow transducers, and hydraulic occluders on the left circumflex coronary artery. The only beneficial effect observed was that the number of arrhythmic beats per minute in the rSOD-treated group was significantly lower (p < 0.05) when compared with a control group after coronary artery reperfusion. Treatment neither increased the amount of recovery of wall thickening in the ischemic zone nor reduced infarct size when expressed either as a percentage of the area at risk or as a function of collateral blood flow in the ischemic zone. For example, infarct size as a percentage of the area at risk was 32.6±5.8%, 37.4±6.4%, 28.3+5.1% in the control, SOD and catalase-, and rSOD-treated groups, respectively. Thus, although treatment with oxygen free radical scavengers invoked a transient reduction in the number of reperfusion arrhythmias, this treatment in conscious dogs failed to improve regional myocardial dysfunction or reduce the amount of necrosis when compared with a control group. The lack of a sustained salutary effect may indicate that longer periods of treatment with free radical scavengers are required in chronic preparations. (Circulation 1989;79:143-153) Coronary artery reperfusion is used with increasing frequency in the therapy of acute myocardial infarction. However, the relatively short time of coronary artery occlusion after which reperfusion can no longer salvage myocardial