Hepatic veno-occlusive disease (VOD) is a common transplant-related complication of stem cell transplantation. There is no safe and proven therapy for established VOD, and attempts have focused on its prevention. Limited studies have suggested that prophylactic use of ursodeoxycholic acid (UDCA) reduced the incidence of VOD. To confirm the preventive effect of UDCA on VOD, we conducted a prospective, unblinded randomized, multicenter study of UDCA involving 132 patients who underwent stem cell transplantation for a variety of disorders. Sixty-seven patients were assigned to the UDCA-treated group, and 65 patients were assigned to the control group. The clinical characteristics of the two groups were similar with respect to primary diagnosis, age, sex, and baseline organ function. The preparative regimen and GVHD prophylaxis did not differ significantly between the two groups. UDCA was highly effective in preventing VOD, which occurred in only 3.0% in the UDCA-treated group, as opposed to 18.5% in the control group (P = 0.0043). There were no adverse effects attributable to UDCA. The initial promising report of a prophylactic effect of UDCA on VOD after stem cell transplantation was confirmed in this prospective study.

Hepatic veno-occlusive disease (VOD) is a common transplant-related complication of stem cell transplantation. There is no safe and proven therapy for established VOD, and attempts have focused on its prevention. Limited studies have suggested that prophylactic use of ursodeoxycholic acid (UDCA) reduced the incidence of VOD. To confirm the preventive effect of UDCA on VOD, we conducted a prospective, unblinded randomized, multicenter study of UDCA involving 132 patients who underwent stem cell transplantation for a variety of disorders. Sixty-seven patients were assigned to the UDCA-treated group, and 65 patients were assigned to the control group. The clinical characteristics of the two groups were similar with respect to primary diagnosis, age, sex, and baseline organ function. The preparative regimen and GVHD prophylaxis did not differ significantly between the two groups. UDCA was highly effective in preventing VOD, which occurred in only 3.0% in the UDCA-treated group, as opposed to 18.5% in the control group (P = 0.0043). There were no adverse effects attributable to UDCA. The initial promising report of a prophylactic effect of UDCA on VOD after stem cell transplantation was confirmed in this prospective study. Am.

Right coronary autoregulation was assessed in 14 open-chest, anesthetized dogs. In Group 1 (n = 5), the left common and right coronary arteries were cannulated and perfused independently. As coronary perfusion pressures varied simultaneously between 70 and 120 mm Hg, right coronary blood flow changed by 48%, whereas left coronary flow changed by 13%. In this pressure range, the autoregulatory closed-loop gain of the right coronary circulation averaged 0.37 ± 0.01, reflecting a modest autoregulatory capability but significantly less than that of the left coronary circulation, 0.78 ± 0.08. In Group 2 (n = 9), only the right coronary artery was perfused, and right coronary venous blood was collected for determining arteriovenous oxygen extraction. Autoregulatory gain was similar to that of Group 1, indicating that collateral flow associated with intercoronary pressure gradients does not mask right coronary autoregulation. Right ventricular myocardial oxygen consumption varied directly with perfusion pressure, ranging from 7.1 ± 1.0 to 2.9 ± 0. 1 Under conditions of stable cardiac function, left coronary blood flow remains relatively constant while coronary perfusion pressure is varied over a wide range.2 " 5 Since the left and right ventricles differ markedly in work performed, oxygen consumption, coronary blood flow, and transmural pressure, differences in autoregulation between the left and right coronary circulations might be expected. 6 The relation between changes in right coronary blood flow and right coronary perfusion pressure has not been specifically investigated, but some data suggest that autoregulation is absent in the right coronary circulation. Murray and Vatner 7 reported that a 34% rise in aortic pressure increased right coronary blood flow 55%. Urabe et al Received June 27, 1986; accepted September 29, 1986. Despite recognized differences between the left and right ventricles, it is not apparent why autoregulatory capabilities of the left and right coronary circulations should be strikingly different. This investigation was conducted to compare simultaneously autoregulation in the canine right and left ventricles. Since right coronary autoregulation was significantly less potent than left coronary autoregulation, additional experiments were conducted to determine the reason for this difference. Materials and MethodsFourteen dogs of either sex, weighing 15 to 24 kg, were anesthetized with sodium pentobarbital, 30 mg/kg i.v. initially, and supplemented as needed to maintain stable anesthesia. After tracheotomy, the dogs were ventilated with room air supplemented with oxygen to maintain normal arterial oxygen tension. A vinyl catheter was positioned in the inferior vena cava via a femoral vein for administration of supplementary anesthetic, heparin, and fluids. A second catheter was advanced into the thoracic aorta via a femoral artery to monitor aortic blood pressure. Left ventricular pressure was measured with a Millar catheter-tip pressure transducer introduced through an incision in the left ...

Responses to norepinephrine (NE) before and after treatment with adenosine deaminase (ADA) were examined in anesthetized dogs. In four dogs repeatable changes in coronary blood flow, myocardial oxygen extraction and consumption, left ventricular +dP/dtmax, and heart rate (HR) were demonstrated during two successive intracoronary infusions of 0.13 micrograms.kg-1.min-1 NE. In eight dogs, the NE-induced hyperemia was decreased from +150 to +67%, the change in myocardial oxygen consumption (MVo2) was attenuated from +177 to +101% by ADA, and the increase in HR was reduced from +28 to +16%. In six dogs, the increase in HR caused by NE before ADA was maintained after ADA by atrial pacing. The NE-induced hyperemia and the increase in MVo2 were again decreased by ADA. Similar results were observed in 12 other dogs with hearts paced at a constant, elevated rate during control as well as during both infusions of NE. In all groups, the O2 extraction response to increased MVo2 increased and the flow response decreased after ADA. In six dogs nitroprusside was infused during NE after ADA. When coronary flow was restored to the same level observed before deaminase, MVo2 was not diminished. These results support a role for adenosine in the coronary functional hyperemia accompanying NE activation of the canine myocardium.

We examined transmurally the right coronary autoregulatory flow response to varied perfusion pressures in 11 anesthetized, open-chest dogs. Right coronary artery flow was measured electromagneticalry, and its transmural distribution was denned with 15-(im radioactive microspheres. Heart rate, mean aortic blood pressure, right ventricular systolic pressure, end-diastolic pressure, and dP/dt_ were constant. At 100 mm Hg, subepicardial flow averaged 0.48 ±0.04 ml/min/g, and subendocardial flow averaged 0.56 ± 0.05 ml/min/g. In contrast to the left coronary circulation, right coronary hypotension did not cause preferential subendocardial ischemia. As right coronary perfusion pressure was decreased from 100 to 40 mm Hg in five dogs, subepicardial and subendocardial flows were reduced similarly by 35-36%. As right coronary perfusion pressure was elevated from 100 to 150 mm Hg in six dogs, right ventricular subepicardial blood flow increased by 31%, whereas 5 a phenomenon known as autoregulation.6 When left coronary perfusion pressure is decreased below the autoregulatory pressure range, regional flow falls more precipitously in subendocardium, 7 "9 and the subendocardial-to-subepicardial flow ratio (endo/epi) reaches approximately 0.3 at complete occlusion of the left coronary artery.8 When left coronary perfusion pressure is increased above the autoregulatory pressure range, the endo/epi ratio increases, 10 indicating that left coronary autoregulation fails first in subendocardium. To date, there have been no reports of regional autoregulatory capability in the right coronary circulation, although we recently found that right coronary artery autoregulation was less potent than left coronary autoregulation." It is possible that the blunted autoregulatory capability of the right coronary circulation has a regional basis like that of the blunted capability Received June 8, 1987; accepted November 2, 1987. of the hyperperfused left coronary circulation. 10 Thus, this investigation was conducted to define transmurally right coronary autoregulatory capability over a wide range of right coronary perfusion pressures. Materials and MethodsEleven mongrel dogs of either sex, weighing 15 to 24 kg, were anesthetized with sodium pentobarbital, 30 mg/kg i.v. initially, and supplemented as needed to maintain stable anesthesia. After tracheotomy, the dogs were ventilated by a respirator (Harvard Apparatus, South Natick, Massachusetts) with room air supplemented with oxygen to maintain normal arterial oxygen tension. A vinyl catheter was positioned in the inferior vena cava through a femoral vein for administration of supplementary anesthetic, heparin, and fluids. A second vinyl catheter was advanced into the thoracic aorta through a femoral artery to monitor aortic pressure. Right ventricular pressure was measured with a catheter-tipped transducer (Millar Instruments, Houston, Texas) inserted through the right jugular vein and across the tricuspid valve. The right ventricular pressure signal was differentiated electronically, and ...