To determine whether there are abnormalities in myocyte excitation-contraction coupling and intracellular Ca2+concentration ([Ca2+]i) homeostasis in pacing-induced heart failure (PF), we measured L-type Ca2+ current ( I Ca,L) and Na+/Ca2+exchanger current ( I Na/Ca) with voltage clamp and measured intracellular Na+ concentration ([Na+]i) and [Ca2+]iwith the use of sodium-binding benzofuran isophthalate (SBFI) and fluo 3 in ventricular myocytes isolated from control and paced rabbits. The peak systolic and diastolic levels and the amplitude of electrically stimulated [Ca2+]itransients (0.25 Hz, extracellular Ca2+ concentration = 1.08 mM) were significantly less in PF myocytes. Also, there was prolongation of the times to peak and decline of [Ca2+]itransients. I Ca,Ldensity was markedly decreased in PF myocytes. I Na/Ca at −40 mV elicited by rapid exposure to 0 Na+ solution with a rapid solution switcher was significantly reduced in PF myocytes, suggesting that the function of the Na+/Ca2+exchanger is impaired in these myocytes. In PF myocytes the decline of the [Ca2+]itransient when the Na+/Ca2+exchanger was abruptly disabled was markedly prolonged compared with the decline in control myocytes, consistent with depressed sarcoplasmic reticulum (SR) Ca2+-ATPase function. RNase protection assay showed decreased levels of Na+/Ca2+exchanger and SR Ca2+-ATPase mRNA in PF hearts, consistent with the function studies. We conclude that the functions of L-type Ca2+channels, Na+/Ca2+exchanger, and SR Ca2+-ATPase are impaired in myocytes from rabbit hearts with failure induced by rapid pacing. These abnormalities result in reduced [Ca2+]itransients and systolic and diastolic dysfunction and appear to account for the abnormal ventricular function observed.

Elevated venous pressure in right heart failure leads not only to an increase in lymph formation but also to progressive resistance in the neck to the return of lymph to the circulation via the thoracic duct. Sequestration of fluid behind the failing heart tends to protect the circulation but at the same time leads to the clinical manifestations of heart failure. The present study was performed on 40 dogs with combined tricuspid insufficiency and pulmonary stenosis. Thoracic duct lymph flow was greatly increased. Pressure was considerably greater in the systemic veins than in the pulmonary vein beyond the right heart obstruction. Lymph flow was substantially enhanced when the thoracic duct was connected to the lower pressure pulmonary veins. Furthermore, direct anastomosis of the thoracic duct to the pulmonary vein resulted in fall in systemic venous pressure, increase in renal excretion of salt and water, and reduction in ascites. These results indicate that alterations in the flow of thoracic duct lymph have important bearing on the manifestations and treatment of right heart failure.

No abstract

A technique is described in which the circulation of the adrenal glands of the dog is completely isolated on the arterial side as well as on the venous side. With this technique the adrenal glands can be perfused in situ and, if desired, in vivo without any interruption of their blood supply and without any direct trauma. The adrenal glands may be perfused with the dog's own blood pumped by the dog's own heart (autoperfusion), or with the blood of another dog pumped by a mechanical pump. It was found that unless both recipient and donor dogs are hypophysectomized, the adrenal glands of the recipient dog are maximally stimulated and are not responsive to large doses of ACTH. If hypophysectomized animals are used, the perfused adrenals secrete small amounts of hydrocortisone and are responsive to very small doses of ACTH. This technique would seem to be an ideal means of studying the direct effect of any agent on the adrenal glands without the interference of other endocrine glands or other organs.

In patients with aortic insufficiency and without disease of the coronary ostia or arteries, the occurrence of chest pain having some or many of the characteristics of cardiac pain due to myocardial ischemia has been ascribed classically to a decrease in the coronary blood flow (1, 2), the aortic insufficiency presumably decreasing the coronary blood flow by lowering the mean aortic diastolic pressure. However, the data available on the effect of aortic insufficiency on the coronary blood flow are contradictory. From acute experiments on the anesthestized dog, Green (3), as well as Green and Gregg (4), concluded that when the aortic insufficiency is marked enough to lower the aortic diastolic pressure, the increase in coronary blood flow occurring during systole does not compensate for the decrease in flow during diastole and the mean coronary flow decreases. On the other hand, Foltz, Wendel, and West (5), from measurements made on anesthetized dogs in which one or two aortic cusps had been torn three or more days previously, concluded that the coronary blood flow was increased over levels usually observed in normal dogs while oxygen consumption was greatly increased over normal levels. Because of the discrepancy in the opinions about the effect of aortic insufficiency on the coronary blood flow, it was thought advisable to reinvestigate this problem. METHODSEight dogs weighing between 17 and 40 kilograms were anesthetized by the intravenous administration of 1 This work was made possible by grants-in-aid from the New York Heart Association, the Sidney A. Legendre Gift and the Charles A. Frueauff Gift.2 Postdoctorate Fellow of the United States Public Health Service.$Fellow of the Dazian Foundation for Medical Research. 4 Research Fellow of the Hudson County (N. J.) Heart Association. 10 ml. per kilogram of weight of a 1 per cent chloralose solution. In the first four dogs the trachea, both common carotid arteries and both external jugular veins were exposed through a midline incision and a Y-shaped glass tube inserted into the trachea. Under artificial respiration, the left hemithorax was opened, the pericardium incised and the heart suspended in a pericardial cradle. The method used to measure and continuously record the output of the left ventricle was a modification of that previously described in this laboratory (6). The proximal ends of the left subclavian artery and brachiocephalic trunk were cannulated. Then the aorta was clamped distally to the subclavian artery so that the blood ejected by the left ventricle was directed into an electromagnetic rotameter (7) and returned to the circulation via both carotid arteries cannulated distally as well as both femoral arteries cannulated proximally and distally. Since the coronary sinus drains blood essentially only from the left coronary artery (8, 9) and since, in a given animal, the coronary sinus blood flow represents a constant portion of the left coronary artery flow (8), measurement of the coronary sinus blood flow was used as a means of studying the left...