Citations

Experiments were designed to determine whether endothelial injury contributes to augmented coronary vascular tone seen during myocardial reperfusion. Canine left anterior descending coronary arteries were exposed to ischemia followed by reperfusion (60 minutes each). Rings (3-4 mm) of the reperfused artery and of normal left circumflex (control) coronary artery segments were prepared. Rings were suspended for isometric force measurement in organ chambers containing modified Krebs' Ringer bicarbonate solution (37 degrees C, 95% O2-5% CO2). Endothelium-independent contractions to KCl and prostaglandin F2 alpha were unaltered after reperfusion. Endothelium-dependent relaxations to nitric oxide, sodium nitroprusside, and isoproterenol were comparable in control and reperfused arteries. However, reperfused coronary arteries contracted with prostaglandin F2 alpha lost the ability to express endothelium-dependent relaxations to aggregating platelets. Reperfused arterial rings also exhibited impaired endothelium-dependent relaxations to acetylcholine, the calcium ionophore A23187, and the platelet-derived compounds ADP and serotonin. Quiescent (noncontracted) reperfused arterial rings exhibited larger contractions than controls when exposed to aggregating platelets. In such quiescent rings, the endothelium-dependent increase in tension to hemoglobin was unaltered after reperfusion. Thus, coronary reperfusion impairs the normal endothelium-dependent relaxations to aggregating platelets and vasoactive drugs. This impairment of platelet-mediated coronary relaxation could help explain the increased vascular tone and tendency toward vasospasm commonly observed after reperfusion of the coronary arteries.

Although urinary sodium excretion is positively influenced by acute changes in renal perfusion pressure, micropuncture studies show highly conflicting results concerning the response of superficial proximal tubule sodium reabsorption to changes in renal perfusion pressure. In the present study, the changes of superficial proximal reabsorption to decreased and increased renal perfusion pressure were determined in rats by an in vivo microperfusion method. In vivo microperfusion was selected as the method to determine the proximal sodium reabsorption because this method made it possible to deliver a constant fluid and electrolyte load to the proximal tubule without the influence of possible changes of glomerular filtration rate. Renal perfusion pressure was decreased from normal pressure by inflating a suprarenal aortic cuff and was increased from the normal level by the occlusion of celiac and mesenteric arteries and the infrarenal aorta. Although fractional excretion of sodium (FENa) in the urine was decreased from 1.24 +/- 0.23% to 0.45 +/- 0.11% (n = 7, p less than 0.01) when renal perfusion pressure was decreased from 125 +/- 6 to 99 +/- 3 mm Hg, absolute tubular reabsorption by the superficial proximal convoluted tubules was not increased (from 4.4 +/- 0.5 to 4.2 +/- 0.3 nl/min/mm, n = 22). When the renal perfusion pressure was elevated from 126 +/- 4 to 149 +/- 4 mm Hg, tubular reabsorption by the superficial proximal tubules was decreased from 4.1 +/- 0.3 to 2.5 +/- 0.3 nl/min/mm (n = 36, p less than 0.01) with an accompanying increase in FENa (from 1.28 +/- 0.24% to 2.29 +/- 0.37%, n = 9, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial pressure, atrial natriuretic factor (ANF), the renin-angiotensin-aldosterone system, and renal hemodynamic functions were examined during and after right ventricular pacing in anesthetized dogs (n = 9). Mean arterial pressure, cardiac output, and renal blood flow decreased during tachycardia while right and left atrial pressures increased. ANF markedly increased during tachycardia but urinary and fractional excretion of sodium were unchanged from control. Plasma renin activity was not increased during pacing despite the decrease in renal perfusion pressure. After tachycardia and restoration of mean arterial pressure to control, ANF declined but remained elevated above control despite a return of atrial pressure to control level. After tachycardia, urinary and fractional sodium excretion increased significantly in the absence of an increase in glomerular filtration rate. These findings support the following conclusions: 1) tachycardia increases ANF in association with increased atrial pressure; however, an elevation of ANF persists following tachycardia despite the absence of the persistent stimulus of elevated atrial pressures; 2) the increase in ANF during tachycardia may contribute to the absence of a decrease in sodium excretion and activation of the renin-angiotensin system that occurs with reduction in renal perfusion pressure; and 3) tachycardia-induced natriuresis may be dependent on an increase in ANF and the maintenance of renal perfusion pressure.

Determinations of pressure, blood flows, and calculated pulmonary vascular resistance were made prior to and during acute individual occlusion of the right and left main branches of the pulmonary artery in random sequence in eight anesthetized, closed-chest dogs witn chronic atrial septal defects. Similar observations were made with occlusion of only the left pulmonary artery in three additional dogs. Obstruction of the pulmonary artery to one lung was immediately followed by a rise in systolic pressure in the right ventricle and pulmonary artery proximal to the obstruction, from an average normal value of 33.1 mm. Hg to an average value of 40.9 mm. Hg (range 32 to 47). This change was not associated with demonstrable systematic effects on right atrial or systemic arterial pressure or on the systemic blood flow. As would be expected, the average calculated ratio of pressure to flow (vascular resistance) across the unoccluded lung was elevated during the obstruction. The resistance value during the occlusion, however, was less than the estimated pressure/flow ratio for this same lung, based on the measurements made prior to the occlusion. This apparent effective decrease in vascular resistance of the unoccluded lung is probably related to dilation of the pulmonary vessels as a result of an increase in intravascular pressure caused by the sudden removal of approximately half of the pulmonary vasculature from the circulation. In spite of the elevation in right ventricular systolic pressure, occlusion of the left pulmonary artery was associated with a slight increase in pulmonary blood flow and a definite increase in the magnitude of the left-to-right shunt across the atrial septal defect, whereas no systematic effects were obtained during obstruction of the right branch in association with the same approximate levels of right ventricular systolic pressure. These data are regarded as further evidence that the preferential shunting of blood from the right lung in the presence of an atrial septal defect of the secundum type is primarily due to the anatomical relation between the opening of these vessels into the left atrium and the position of the defect in the atrial septum. Furthermore, they emphasize the importance of dynamic factors, related to the manner, site, and direction in which the pulmonary venous blood drains into the left atrium, as important determinants of the left-to-right shunt via such defects.

Systemic and pulmonary blood flows and pressures were determined in anesthetized closed-chest dogs with chronic atrial septal defects and in dogs with intact cardiac septa. In the former animals, graded obstruction of the main pulmonary artery associated with right ventricular systolic pressures of more than 80 mm. Hg was produced without evidence of failure of the right side of the heart. A considerable decrease in the magnitude of the left-to-right shunts and an increase in the size of the right-to-left shunts occurred; these changes were associated with only minor changes in filling pressure of the right ventricle, and systematic changes in systemic arterial pressure did not appear. Analysis of right atrial pressure pulses suggested the development of an increased force of contraction of the right atrium and no evidence of tricuspid regurgitation under these circumstances. In contrast, partial obstruction of the main pulmonary artery in the dogs with intact cardiac septa, so as to increase the right ventricular systolic pressure to more than 60 mm. ITg, was associated with pronounced increases in mean right atrial pressure and striking decreases in cardiac output and systemic arterial pressure. The pressure recordings from the right atrium and indicator-dilution curves demonstrated the development of significant tricuspid regurgitation. The deterioration of right ventricular function in dogs with intact cardiac septa appears to be related to overdistention of the right ventricle and possibly also to a disproportionate reduction in coronary blood flow to the myocardium caused by a decrease in systemic arterial pressure and the concomitant increase in resistance to coronary venous drainage from the right side of the heart due to the increased right atrial and right ventricular pressures. It is concluded that under the conditions of these studies, an atrial septal defect provides a considerable increase in resistance to the heinodynamic effects associated with right ventricular hypertension caused by acute partial obstruction of the main pulmonary artery. The possible duration of this beneficial effect beyond the 33 to 160 minutes of observation in these studies has not been explored.

Indicator-dilution curves were recorded simultaneously from the left atrium and the femoral artery during injections of indocyanine green into the left ventricle in normal dogs and in dogs with chronic mitral regurgitation. A study was made-without the use of thoracotomy-of the effect of the following factors on the amount of early appearing indicator detected in the left atrium: (a) the timing of the injection of indicator in relation to the cardiac cycle, (b) the position of the injecting catheter in the left ventricle, and (c) the position of the sampling catheter in the left atrium. It was found that the time and site of the injection into the left ventricle had little effect on the amount of early appearing dye detected in the left atrium and that, although the position of the sampling catheter in the left atrium was important, reproducible results were attained when the sampling site was restricted to a region in close proximity to the mitral valve. A close correlation was demonstrated between the volume of regurgitation determined independently on a hydraulic basis and the volume estimated from the fraction of early appearing indicator detected in the left atrium. It is concluded that further work with this upstream-sampling technique is justified in order to study its possibilities as a practical method for detecting and quantitating mitral regurgitation in human beings.

The manner in which the administration of epinephrine, norepinephrine, isoproterenol, and atrophic modifies the cardiovascular response to exercise has been studied in 12 dogs. In control observations, exercise increased the cardiac output by 116 per cent, the heart rate by 102 per cent, and the stroke volume by 8 per cent. When epinephrine was infused during identical exercise, the cardiac output was similar; however, the stroke volume was increased by 50 per cent. During infusion of norepinephrine, the cardiac output was reduced by 11 per cent compared with that during control exercise, and the stroke volume was increased by 25 per cent. With isoproterenol, the cardiac output exceeded that during control exercise, but the stroke volume was unchanged. Prior to administration of atropine, the cardiac output at rest averaged 4.2 L. per minute. After injection of atropine, the cardiac output averaged 3.7 L. per minute, the heart rate increased from 121 to 249 beats per minute, and the stroke volume decreased from 35 to 15 ml. Before atropinization, the cardiac output, heart rate, and stroke volume during exercise were increased by 95, .90, and 2 per cent over the resting values; after atropinization, the corresponding increases were 110, 7, and 100 per cent. Thus, while cardiac output during exercise normally is regulated mainly by changes in the heart rate, the stroke volume may make a major contribution under other circumstances.

The effect of exercise on the pulmonary circulation was studied in a group of 6 intact dogs and in a second group of 4 subjected to ligation and division of the left pulmonary artery. Observations were made with the dogs standing and running on a horizontal treadmill up to the maximal speed they could maintain for periods of at least 2 minutes, usually 12 or 14 km./hr. Continuous records were made of the difference in pressure between the main pulmonary artery (PA) and a pulmonary-artery wedge (PAW) position. Cardiac output was determined by the indicator-dilution method, with injection of indocyanine (cardiogreen) dye into the main pulmonary artery and continuous sampling from the root of the aorta. The mean transit time of indicator betweell the pulmonary and aortic valves was obtained from the dilution curves, a correction being made for the transit time through the sampling apparatus. From these measurements the blood volume of the lungs and left heart chambers was derived. In the intact dogs, cardiac output increased approximately threefold from rest to severe exercise. There was an increase of only 12 per cent to 50 per cent in PA minus PAW pressure. Thus a continued fall occurred in pulmonary vascular resistance. The blood volume of the lungs and left heart of 3 intact dogs was measured. In 2 it did not change through the range of activity, and in the third the increase with maximal exercise was 18 per cent. The dogs with ligated left pulmonary artery also showed a threefold increase in output with severe exercise. Since the entire output passed through a single lung, the effect on the pulmonary vessels was comparable to that of a sixfold increase in output in a normal dog. Despite such large flows, in 3 of 4 dogs the difference between PA and PAW pressure rose only 37 per cent to 50 per cent. The volume of blood in the lungs and left heart was unchanged between rest and 8 km./hr., and at higher speeds showed a 0 per cent to about 20 per cent increase.

1. In the anesthetized dog, end-diastolic, end-systolic and stroke volumes for the left ventricle have been calculated according to the method of Holt from dilution curves recorded at the aortic root. For heart rates of less than 120 beats per minute, the catheterdensitometer systems used gave 90 to 95 per cent of the true concentration in the aortic root at the end of diastole. 2. Average volumes of 2.96, 1.63 and 1.33 ml./Kg. of body weight were calculated for each of these parameters. The interindividual and intraindividual variations about these means amounted to ± 30 to 50 per cent. 3. In approximately 15 per cent of the dilution curves the concentration of dye in the aortic root during early systole (phase of maximal ejection) showed a transient, markedly low value compared with that of the end of diastole. This can be explained only on the basis of the preferential ejection from the heart in early systole of the undyed, newly entering blood from the left atrium, which had mixed poorly with the residual volume of the ventricle. Qualitative inspection of cineangiograms confirmed this impression and demonstrated that a residuum of contrast medium failed to mix with the incoming blood from the left atrium. 4. In addition, there is evidence for the possibility of overestiination of stroke volumes from dilution curves recorded immediately proximal to the injection chamber. 5. Incomplete mixing of the left artial blood with the residual volume of the ventricle precludes accurate quantitation of the changes of volume in the ventricle by the simple formulas proposed by previous authors. This phenomenon may serve to explain the considerable variability that is found in the present study and in the literature.

Measurements of stroke volume were made in dogs during graded exercise on a horizontal treadmill up to the maximal exercise which they could maintain for 2 to 3 minutes. Eleven series of experiments were performed on 7 dogs. The cardiac output was measured by the indicator-dilution technic and the heart rate was measured from the aortic pressure tracing. At all grades of exercise, there was little or no change in stroke volume. Even with severe exercise, when the cardiac output had increased from 1.5 to 3.5 (average, 2.4) times the values obtained with the dog standing at rest, the stroke volume showed less than 5 per cent change over resting values in 5 experiments on 4 dogs, while in the remainder the increases were 8, 11, 11, 14, 15, and 19 per cent. Thus, the increase in cardiac output in the untrained exercising dog is almost directly proportional to the increase in heart rate. This is in contrast to other situations, such as the combination of exercise with infusion of catecholamines, where an increase in stroke volume may make an important contribution to the increase in cardiac output.