Ralph E. Purdy

Cardiac function after eight hour storage by using polyethylene glycol hemoglobin versus crystalloid perfusion.

Efforts to extend myocardial preservation for transplantation by crystalloid perfusion have been limited by edema and compromised function. We hypothesized that hypothermic perfusion preservation with a polyethylene glycol (PEG) conjugated hemoglobin solution may extend preservation times. The purpose of this study was to compare cardiac function after continuous perfusion by using a hypocalcemic, normokalemic crystalloid perfusate with and without the addition of PEG-hemoglobin (Hb). The hearts of 20 anesthetized and ventilated New Zealand White rabbits were harvested after cold cardioplegic arrest. Group I (n = 10) hearts were continuously perfused with a hypocalcemic, normokalemic 3% bovine PEG-Hb solution at 20°C and 30 mm Hg for 8 hours. Group II (n = 10) hearts were continuously perfused with an identical crystalloid solution without PEG-Hb for 8 hours under the same conditions as group I hearts. Cardiac function was measured with a left ventricular force transducer after transfer to a standard crystalloid Langendorff circuit at 37°C and an aortic root pressure of 59 mm Hg. After 8 hours of perfusion preservation, heart rate was similar for groups I and II (p = not significant [NS]). Coronary blood flow after and during preservation was similar between PEG-Hb and crystalloid preserved hearts (p = NS). Left ventricular developed pressure, peak dP/d t, and peak −dP/d t were superior in hearts preserved with PEG-Hb. Percent water of total ventricular weight was 82.0% for group I and 81.6% for group II (p = NS). Continuous perfusion preservation of rabbit hearts for 8 hours with a hypocalcemic normokalemic PEG-Hb based solution at 30 mm Hg and 20°C yields left ventricular function that is superior to perfusion with a similar crystalloid solution without PEG-Hb, despite similar myocardial edema and coronary flow. Extended cardiac perfusion preservation with this PEG-Hb based solution deserves further study, including comparison with traditional cardioplegic preservation solutions.

Enhancement of the pressor response to norepinephrine by angiotensin in the conscious rabbit

The pressor interactions between angiotensin II and norepinephrine were investigated in conscious New Zealand white rabbits receiving a low sodium diet. Angiotensin II was administered continuously by intraperitoneal osmotic pumps in a subpressor dose so as to avoid the potentially confounding effects of experimentally-induced hypertension. Norepinephrine challenges were given as a series of graded intravenous boluses. During the 3 days of study the baseline blood pressure in the angiotensin-treated rabbits (n=10) did not differ from that in controls (n=10) whose intraperitoneal pumps contained only diluent. After 24 hours the systolic and diastolic blood pressure responses to norepinephrine in the angiotensin-treated group were, on average, 45% and 30% higher than in the controls; after 72 hours, they were 46% and 34% higher. Although the pressor amplitudes were increased by angiotensin II, they were not prolonged. Thus, facilitation by the subpressor angiotensin II of the blood pressure responses to norepinephrine did not seem dependent upon alterations in endogenous sympathetic mechanisms or the uptake of norepinephrine; nor could it be explained by sodium retention. It is possible that angiotensin II exhibits its effect by enhancing contractile responsiveness to norepinephrine at the postreceptor level.

Recovery of cardiac function after standard hypothermic storage versus preservation with Peg-hemoglobin.

Preservation of the heart for transplantation after infusion of cardioplegia and extirpation of a cardiac allograft results in an ischemic insult to the myocardium. This ischemic insult may lead to a loss of function in the transplanted heart. Hypothermic perfusion preservation with an oxygen hemoglobin carrying solution may avert ischemic injury and lead to improved recovery of cardiac function. The purpose of this study was to compare cardiac function after 8 hours of continuous hypothermic perfusion with a unique polyethylene-glycol-hemoglobin (PEG-Hb) solution to hearts preserved by 4 hours of hypothermic ischemic storage. Freshly extirpated hearts served as functional controls. The hearts of 26 anesthetized and intubated New Zealand white rabbits were harvested after cold cardioplegic arrest. Group I (n = 12) hearts were perfused with a PEG-Hb solution at 20°C and 30 mm Hg for 8 hours. PO2 was maintained ≥ 500 mm Hg. Group II (n = 7) hearts were preserved by cold ischemic storage for 4 hours at 4°C. Group III (n = 7) were tested immediately after harvest. Left ventricular (LV) function was measured in the nonworking state at 15 minutes, 1 hour, and 2 hours after transfer to a standard crystalloid Langendorff circuit. Measurement of LV developed pressure, peak + dP/dt and −dP/dt revealed a superior trend between Group I and Group II hearts in comparison with freshly extirpated hearts. Heart rate was similar among all groups throughout testing (p = ns). Coronary blood flow was not significantly different between groups. Continuous perfusion preservation of rabbit hearts for 8 hours with PEG-Hb solution at 30 mm Hg and 20°C yielded LV function that was similar to 4 hours of ischemic hypothermic storage. Furthermore, return of cardiac function after 8 hours of perfusion preservation using this PEG-Hb solution may be superior to that obtained in freshly extirpated hearts. These data suggest that some recovery of myocardial function may occur during perfusion preservation with this PEG-Hb solution after the ischemic insult of cardioplegic arrest. Continuous perfusion preservation using this PEG-Hb solution deserves further investigation in large animal transplant models.

Aldosterone: Possible Roles in Sustaining Essential Hypertension and in Determining Response to Antihypertensive Treatment

A clear role for aldosterone in sustaining hypertension was first described with the syndrome of primary aldosteronism, a condition in which this mineralocorticoid hormone is secreted autonomously by adenomatous or hyperplastic adrenal glands. It has been presumed that this form of hypertension is sustained by aldosterone-mediated sodium and water retention, but there has been no consistent evidence for volume expansion. And, although spironolactone, a specific antagonist of aldosterone’s mineralocorticoid action, normally corrects the metabolic abnormalities of primary aldosteronism, it does not restore blood pressure to normal levels in all cases.