Ibrahim M. Khatri

Quantitation of portasystemic shunting from the splenic and mesenteric beds in alcoholic liver disease

Abstract The fraction of portal venous inflow shunted through portasystemic collaterals was computed by comparing the area of an isotope dilution curve recorded from the hepatic vein after injection into the superior mesenteric or splenic artery with that after injection into the hepatic artery. In seven normal subjects no shunting could be detected, but in forty patients with alcoholic liver disease shunting of mesenteric flow averaged 61.9 per cent and splenic flow 80.1 per cent. In nine of twenty-seven complete studies, there was a discrepancy of greater than 40 per cent between mesenteric and splenic shunting, with splenic shunting usually but not always predominating. No significant relationship between per cent shunting and hepatic blood flow or portal pressure was found. Repeat studies after three to eighteen months in three patients showed progressive increase in the fraction of shunted portal flow. These data indicate that portasystemic collateral circulation may develop independently in the mesenteric and splenic beds in portal hypertension. Furthermore, establishment of an effective collateral circulation in patients with alcoholic liver disease does not necessarily deprive the liver of blood flow or decompress the portal vein.

Cardiac and peripheral vascular effects of digitalis in clinical cardiogenic shock

Abstract The hemodynamic effects of cardiac glycosides were studied in 13 patients with cardiogenic shock. Intravenous administration of ouabain, deslanoside, or digoxin produced a prompt pressor effect which was characterized by increases in systemic vascular resistance and tension time index and no change or increase in right atrial pressure (RAP) and left ventricular enddiastolic pressure (LVEDP). Acute pulmonary edema developed during this period in one patient. During the later phase, 15 to 60 minutes after infusion of digitalis, there were increases in the maximum rate of rise of left ventricular pressure (LV dp dt ), mean systolic ejection rate, and left ventricular stroke work usually with a fall in RAP or LVEDP. Despite the evidence of improved myocardial function, cardiac output (CO) was not significantly increased and was always lower than that attained during infusion of isoproterenol. It is concluded that digitalis is not very effective by itself in restoring blood flow in cardiogenic shock and that the early peripheral vasoconstrictor effect following intravenous administration may be deleterious in some patients.

Hepatic blood flow in alcoholic liver disease measured by an indicator dilution technic

Abstract Indicator dilution curves recorded from hepatic venous blood after selective injection of I 131 albumin into the hepatic artery were used to calculate hepatic blood flow in four normal subjects and forty-five patients with alcoholic liver disease. In fourteen patients with acute alcoholic hepatitis, hepatic blood flow was significantly higher (average 1,170 ± 94 [SEM] ml/minute/M 2 ) than in normal subjects (average 669 ± 62 ml/minute/M 2 ) or in twenty-four patients with chronic alcoholic liver disease (average 870 ± 76 ml/minute/M 2 ). In seven patients with preterminal hepatic failure hepatic blood flow averaged 982 ± 202 ml/minute/M 2 . The hepatic fraction of cardiac output averaged 24.6 per cent in normal subjects and 25.9 per cent in those with alcoholic hepatitis, but it was significantly reduced in patients with chronic liver disease (average 19.3 per cent) and hepatic failure (average 20.1 per cent). Hepatic plasma volume also was higher in patients with alcoholic hepatitis (average 436 ml) than in the normal subjects (average 364 ml), the patients with chronic alcoholic liver disease (average 365 ml) or the patients with hepatic failure (average 336 ml). Despite the normal or high hepatic blood flow in most patients with alcoholic liver disease, abnormally high hepatic venous oxygen saturation was indicative of reduced splanchnic oxygen consumption in patients with alcoholic hepatitis and in those with hepatic failure compared to the normal subjects. A significant correlation between arteriovenous oxygen difference and hepatic albumin mean transit time suggests that intrahepatic shunting of oxygen could be a factor contributing to impaired hepatic function.

Studies in clinical shock and hypotension: VI. Relationship between left and right ventricular function

Left ventricular end diastolic (LVEDP) and mean right atrial (RAP) pressures were recorded simultaneously in 30 patients with shock (14 acute myocardial infarction, 10 acute pulmonary embolism or severe bronchopulmonary disease, and 6 sepsis). Myocardial infarction was characterized by a predominant increase in LVEDP, pulmonary disease by a predominant increase in RAP, and sepsis by a normal relationship between LVEDP and RAP. In all three groups a significant positive correlation was noted between RAP and LVEDP, with the regression line in cor pulmonale deviated significantly toward the RAP axis and the regression line in myocardial infarction exhibiting a zero RAP intercept at an elevated LVEDP.Low cardiac outputs with elevated LVEDP in myocardial infarction indicated severe left ventricular failure. Low outputs with elevated RAP in cor pulmonale were consistent with right ventricular overload. Although cardiac outputs often were normal in sepsis, low outputs with elevated cardiac filling pressures in some patients were consistent with a hemodynamic or humoral-induced generalized depression of cardiac performance.Vasoconstrictor and inotropic drugs often produced a functional disparity between the two ventricles, with the gradient between LVEDP and RAP increasing, apparently because of an increase in left ventricular work or an inadequacy of left ventricular oxygen delivery. Acute plasma volume expansion with dextran in patients with pulmonary vascular disease resulted in a somewhat more rapid rise in RAP than in LVEDP. In septic and myocardial infarction shock, however, LVEDP and RAP usually rose proportionally, with the absolute rise of LVEDP surpassing that of RAP. Although the absolute level of the central venous pressure thus may not be a reliable indicator of left ventricular function in shock, changes in venous pressure during acute plasma volume expansion should serve as a fairly safe guide to changes in LVEDP.

Direct and reflex cardiostimulating effects of hydralazine.

Increased cardiac output and heart rate after administration of hydralazine have been attributed to reflex activation of the cardiac sympathetic nerves secondary to the decrease in arterial pressure. However, some studies suggest that hydralazine has an additional direct cardiostimulatory effect. The present study was designed to investigate this possibility. Mean arterial pressure, percent change in myocardial contractile force using a Walton-Brodle strain gauge and heart rate were measured in eight open chest dogs anesthetized with sodium pentobarbital. After intravenous administration of hydralazine, 20 mg, myocardial contractile force increased on average by 27 percent and heart rate by 7 percent; mean arterial pressure decreased less than 10 percent. The same reduction of mean arterial pressure with sodium nitroprusside resulted in increases of only 10 percent in myocardial contractile force and 2 percent in heart rate. The differences between the drugs were statistically significant for heart rate (P < 0.05) and myocardial contractile force (P < 0.01). After reductions in mean arterial pressure exceeding 10 percent, the increases in heart rate and myocardial contractile force with either hydralazine or sodium nitroprusside were insignificantly different. Direct injection of 0.8 mg of hydralazine into a coronary artery in four dogs consistently increased myocardial contractile force in the area perfused whereas administration of sodium nitroprusside even in large doses exerted no local inotropic activity. The local effect of hydralazine was blocked by intravenous administration of propranolol. These results suggest that the increase in myocardial contractile force and heart rate after administration of hydralazine is the result not only of a reflex response to a decrease in blood pressure, as occurred with sodium nitroprusside, but also of direct beta adrenergic stimulation of myocardium.

Leukocyte intracellular cations in hypertension: Effect of antihypertensive drugs.

Leukocyte (WBC) cations were determined in 32 normotensive control subjects and in 47 agematched patients with uncomplicated hypertension. The intracellular concentration of sodium (Na+) which averaged 25.5 mEq./Kg. wet cell weight (wcw) in the hypertensive patients was significantly higher (P <.01) than in the control subjects (average 19.7 mEq./Kg. wcw). Elevated WBC Na+ was observed only in the hypertensive patients under age 50 years. WBC potassium, magnesium, and percentage water content were not significantly different in hypertensive patients as compared to the control subjects. The finding of an increased intracellular Na+ content in hypertensive patients is consistent with recent observations relating the extracellular/intracellular Na+ gradient to vascular smooth muscle tension and to the control of the peripheral vascular resistance. WBC cations also were determined after treatment with hydrochlorothiazide, hydralazine, reserpine, or alpha methyldopa. Hydrochlorothiazide was associated with a reduction in WBC sodium content (P < .01). Reserpine also was associated with a lesser fall in WBC sodium (P < .05). Cell water content decreased slightly after hydrochlorothiazide (P < .05), but increased slightly following reserpine (P < .05). Changes in WBC, sodium, or water were not significant following alpha methyldopa or hydralazine. None of the drugs were associated with changes in WBC potassium or magnesium, although serum potassium concentration decreased significantly (P < .05) with hydrochlorothiazide.

Hemodynamic Changes During Sleep in Hypertensive Patients

Hemodynamic studies were carried out during nonsedated all-night sleep on 14 patients with established hypertension. The significant changes from awake control values were as follows: mean arterial pressure fell 7.3% in stages I and II sleep and 8.8% in deep (stages III and IV) sleep; cardiac output decreased 10.3, 9.8, and 8.8% in stages I, II, and III and IV sleep, respectively; heart rate fell 4% in stage II sleep. Total peripheral resistance was not significantly altered. These hemodynamic responses during sleep were similar both quantitatively and qualitatively to those previously found in normal subjects. A small difference, which was of questionable significance, was noted between the two groups of subjects with respect to rapid eye movement sleep. While these observations do not disprove a primary neurogenic component in hypertension, they do not support such an hypothesis.

Systemic Vasoconstrictor and Renal Vasodilator Effects of PLV-2 (Octapressin) in Man

The systemic and renal hemodynamic effects of PLV-2 (octapressin) were studied in patients with hypotension or decompensated cirrhosis of the liver. Low doses (0.004 to 0.02 units/min) increased renal blood flow (indicator-dilution technique), reduced renal vascular resistance, and produced a slight increase in arterial pressure and systemic vascular resistance. Higher doses (0.1 to 0.5 units/min) produced a sharp increase in arterial pressure and systemic resistance while renal resistance increased moderately and renal blood flow usually was maintained above control levels. Renal fraction was increased at all dose levels. The increased renal blood flow was accompanied by more rapid intrarenal dye transit time and slight increase in renal extraction ratio of paraaminohippurate suggesting a rise in cortical blood flow. It is concluded that PLV-2 in small doses produces renal vasodilatation and in larger doses preferential extra-renal vasoconstriction resulting in redistribution of blood flow to the kidney.

Bedside catheterization of the left ventricle.

Abstract Left ventricular catheterization at the bedside without the aid of fluoroscopy was accomplished successfully in 38 of 46 acutely ill patients with the use of a specially curved polyethylene catheter introduced percutaneously in the femoral artery. The procedure could be accomplished quickly and with no serious complications. This simplified technique may make left ventricular pressure monitoring a practical diagnostic and therapeutic guide in certain patients with shock.

Mechanism of exercise hypotension after sympathetic blockade.

Blood pressure measured immediately after a brief period of upright leg exercise was considerably lower than the resting standing blood pressure in 38 hypertensive patients treated with guanethidine or debrisoquin. The hemodynamic mechanism of this hypotension after exercise was studied in 6 hypertensive patients given guanethidine intravenously and in 16 patients treated with effective oral doses of guanethidine or debrisoquin. Intravenous and oral drug treatment blocked the reflex forearm vasoconstriction that normally occurs during leg exercise. Although supine exercise was associated with a modest fall in arterial pressure from hypertensive levels, the most dramatic effects of the blocking agents on the response to exercise were observed when patients were in the upright position. Blood pressure rose from normal to above normal levels during exercise and fell promptly to below resting levels when leg movement was stopped. Upright leg exercise in the treated patients was accompanied by a large increase in cardiac output and a sharp fall in leg volume. Immediately after exercise, cardiac output fell moderately and leg volume rapidly increased. These studies suggest that alterations in the hemodynamic response to exercise induced by sympathetic blocking agents are due both to inhibition of reflex arteriolar constriction and to large passive shifts in blood volume that occur in the upright position as a result of blockade of venous reflex adjustments. Hypotensive symptoms related to exertion probably result from the combined effects of gravitational pooling after exercise and a persistently low peripheral vascular resistance. These symptoms can promptly be corrected by reinstitution of leg exercise. It is suggested (1) that immediately after upright leg exercise the blood pressure is more sensitive to mild degrees of adrenergic blockade than when patients are in the resting standing position and (2) that the postexercise blood pressure may serve as a more reliable guide to adjustment of the dose of sympathetic blocking agents in patients with hypertension.