Red cell survival in patients with nonalcoholic liver cirrhosis before and after distal splenorenal shunt

We previously reported severe hemolysis in one patient immediately after distal splenorenal shunt (DSRS). The purpose of the present study was to evaluate changes in red cell survival after DSRS. In ten patients with nonalcoholic cirrhosis in whom DSRS was performed for esophageal varices, red cell survival and splenic quantitative hemodynamic studies were performed before and after DSRS. The splenic venous blood flow per unit volume (flow/volume ratio) was calculated. The red cell survival was significantly (P<0.05) shortened after DSRS; the apparent half-life survival time (T_1/2) before and after DSRS was 24.6±5.9 (mean±SD) and 16.3±8.5 days, respectively. After DSRS, the spleen volume was significantly (P<0.05) decreased, whereas the splenic venous blood flow was slightly increased. The spleen flow/volume ratio was significantly (P<0.05) increased after DSRS. There was a significant and negative correlation (r=−0.684,P<0.05) between the postoperative percentage change in T_1/2 and the spleen flow/volume ratio. These findings suggest that the red cell survival period is significantly decreased after DSRS in patients with nonalcoholic cirrhosis, and that the increased splenic blood flow per unit spleen volume after DSRS may play an important role in the hemolytic reaction in the spleen after this procedure.     

Effect of distal splenorenal shunt plus splenopancreatic disconnection on glucose and amino acid metabolism

BACKGROUND/AIMS: The Warren-Zeppa distal selective splenorenal shunt (DSRS) is aimed at decompressing esophageal varices by a distal splenorenal shunt, at the same time ligaturing left gastric, gastroepiploic and umbilical veins. In the long-term follow-up the loss of shunt selectivity was observed in several cases. Therefore, Inokuti and Warren reported splenopancreatic disconnection (SPD) to prevent splenic collaterals from stealing portal venous blood. METHODOLOGY: This report presents metabolic data (K-glucose, IRI in iv-GTT, Fischer ratio) of 10 cirrhotic patients operated with DSRS plus SPD. RESULTS: K-glucose of iv-GTT was improved from 2.3 +/- 0.2 to 2.5 +/- 0.2. Fischer ratio was also improved from 1.58 to 2.0 after the operation. IRI behavior tends to be lower after operation as a result of devascularlization of the collateral circulation by the selective shunt. CONCLUSIONS: From these results it seems that DSRS+SPD has favorable effects on glucose and amino acid metabolism.     

New trends in surgical treatment for portal hypertension

A number of surgical procedures have been developed to manage esophageal varices. Broadly, these can be classified as shunting and non-shunting procedures. While total shunt effectively reduces the incidence of variceal bleeding, it is associated with a high risk of hepatic encephalopathy. The distal splenorenal shunt (DSRS), a selective shunt, was developed by Warren in 1967 to preserve portal blood flow through the liver while lowering variceal pressure. The hope was that both bleeding and hyperammonemia would be prevented. The DSRS effectively prevents rebleeding, but still carries a risk of hyperammonemia. We improved the DSRS procedure by additionally performing splenopancreatic disconnection (SPD, i.e. skeletonization of the splenic vein from the pancreas to its bifurcation at the splenic hilum) and gastric transection (GT, i.e. transection and anastomosis of the upper stomach with an autosuture instrument). An alternative to shunting was developed by Sugiura and Futagawa in 1973. Esophageal transection (ET) divides and reanastomoses the distal esophagus and devascularizes the distal esophagus and proximal stomach; splenectomy, selective vagotomy, and pyloroplasty are performed concomitantly. DSRS was more effective than ET in preventing recurrence of esophageal varices, but was associated with a higher incidence of hyperammonemia. The incidence of hyperammonemia in patients who underwent DSRS with SPD plus GT was significantly lower than that in patients who underwent DSRS alone or those who underwent DSRS with SPD. In conclusion, there are various surgical treatments for esophagogastric varices. Distal splenorenal shunt with SPD plus GT is considered an adequate treatment for patients with esophagogastric varices.     

Results of distal splenorenal shunt with versus without splenopancreatic disconnection

From December 1973 to December 1987, we performed a distal splenorenal shunt (DSRS) in 112 cases of portal hypertension, including 107 with postnecrotic liver cirrhosis and 5 with idiopathic portal hypertension (IPH). They comprised about 50% of our surgical cases with esophageal varices. In 1981, we modified our operative procedure towards a more extended splenopancreatic disconnection (SPD) in order to prevent the "stealing" of the shunt through the pancreatic vein. In one group of 69 patients who underwent DSRS alone, the operative mortality was 2.9%; postoperative encephalopathy was seen in 17.4%, late hepatic failure in 40.6%, and recurrence of varices in 4.3%. In the other group, 43 patients who underwent DSRS with SPD, there were no operative deaths, no encephalopathy (better than DSRS alone at p less than 0.05), and late hepatic failure was seen in only 9.3% (better than DSRS alone at p less than 0.025), while the recurrence rate of 7% was the only statistical increase. These data show that DSRS + SPD can improve chances of survival.     

Dynamic fluctuations in blood and spleen radioactivity: splenic contraction and relation to clinical radionuclide volume calculations

Alterations in the blood radioactivity affect ventricular volume calculations using count-based radionuclide ventriculography. To study this phenomenon, the effect of time, posture and supine exercise on blood radioactivity, red blood cell count and splenic radioactivity was evaluated. The red blood cell count, and blood, splanchnic and splenic radioactivity remained stable in five patients studied at rest in the supine position. On standing, blood radioactivity increased 10 +/- 3% (standard error of the mean), and abdominal radioactivity decreased 14.5 +/- 6.5% (both p less than 0.05). In 10 patients, splenic radioactivity decreased after supine exercise by 49 +/- 7%, while blood radioactivity increased 10.5 +/- 1.5% and red blood cell count increased 7.5 +/- 1.5% (all p less than 0.001). Splenic radioactivity increased gradually after exercise and decreased after a second exercise period. In the exercising patients, blood radioactivity increased by 14.5% and correlated with an increase in the red blood cell count (r = 0.57, p = 0.01, 19 samples from 10 patients). Reduction in splenic radioactivity also correlated with the increase in red blood cell count (r = -0.51, p = 0.025). The data demonstrate splenic shrinkage in human beings and an inverse relation between changes in splenic and blood radioactivity. These dynamic fluctuations emphasize the need for simultaneous blood sampling for accurate calculation of left ventricular volume and high-light the importance of regional volume shifts during exercise.     

The Effects of Endoscopic Sclerotherapy Combined with Transhepatic Variceal Obliteration on Portal Hemodynamics

We studied the effects of endoscopic sclerotherapy with transhepatic variceal obliteration on portal hemodynamics in 20 patients with cirrhosis (six with a spontaneous splenorenal shunt and 14 without it). Portal venous flow 1 month after combined therapy (measured by pulsed Doppler flowmeter) was significantly increased compared with that before therapy (n = 20, 843 +/- 339 vs. 669 +/- 253 ml/min, p less than 0.001). Portal vein catheterization and portal venous flow measurement were repeated 18 months after therapy in eight patients without a splenorenal shunt before therapy and in two patients with a splenorenal shunt before therapy. Two of the former developed a splenorenal shunt. In these 10 patients, portal venous flow before, one month, and 18 months after therapy was 617 +/- 219, 784 +/- 227, and 720 +/- 224 ml/min, respectively, and in 8 of 10 patients the portal venous flow at 18 months remained similar to the values at one month. Portal vein pressures were not significantly elevated 18 months after therapy (35.4 +/- 6.4 vs. 33.6 +/- 5.1 cm H2O) and the mean portal vein pressure change was 2.75 cm H2O (range -6 to +7.5 cm H2O). To summarize, portal venous flow was significantly increased one month after combined sclerotherapy in cirrhotics, the portal venous flow at 18 months remained similar to the values at 1 month in most patients, and the change in portal vein pressure after therapy was small.     

Beta-blockade with propranolol and hepatic artery blood flow in patients with cirrhosis

In patients with cirrhosis and portal hypertension, propranolol administration reduces heart rate and cardiac output and diminishes portal pressure and collateral blood flow. However, there is little information on the possible effects of propranolol on hepatic artery blood flow. The present study addressed this question in 12 cirrhotic patients with end-to-side portacaval shunt, in whom all of the liver blood flow represents the hepatic artery blood flow. Hepatic artery blood flow (continuous infusion of indocyanine green), cardiac output (thermal dilution), heart rate and mean arterial pressure were measured before and 20 min after the intravenous infusion of 10 to 15 mg of propranolol. beta-Adrenergic blockade caused a significant reduction of cardiac output (from 9.1 +/- 2.1 to 7.1 +/- 1.4 liters per min, p less than 0.001) (mean +/- S.D.) and heart rate (from 85 +/- 10 to 71 +/- 7 beats per min, p less than 0.001), and a significant increase of systemic vascular resistance (from 9.0 +/- 2.1 to 11.7 +/- 2.7 mmHg per liter per min, p less than 0.001), whereas mean arterial pressure did not change (77 vs. 78 mmHg). Propranolol significantly reduced hepatic artery blood flow (from 0.65 +/- 0.20 to 0.55 +/- 0.14 liters per min, p less than 0.01). However, reduction of hepatic artery blood flow (-12.9 +/- 7.3%) was significantly less than reduction of cardiac output (-21.1 +/- 5.2%, p less than 0.01). As a result, the fraction of the cardiac output delivered to the liver was significantly greater after propranolol (8.0 +/- 1.7%) than before (7.3 +/- 1.7%, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

An ultrasonic duplex system facilitates detection of portal hemodynamic changes following selective shunts for esophageal varices

We used an ultrasonic duplex system (US system) to assess portal hemodynamics in 52 patients with liver cirrhosis and esophageal varices, who underwent 2 types of distal splenorenal shunt (DSRS), conventional DSRS (group A, 8 patients) or DSRS with splenopancreatic disconnection (group B, 44 patients). The portal blood flow rate (PBF) was determined in 64 out of 70 patients (91.4%) and the shunt flow rate (SVF) in 39 out of 42 patients (92.9%) who had angiographically confirmed patent portal vein and shunt vein, during the peri- and postoperative period. In group A, a remarkably small amount of postoperative PBF (193 ml/min) and a concomitant increase in SVF (1039 ml/min) were evident. Such ultrasonic findings were compatible with a reduction in portal vein diameter, in accordance with the poor portal perfusion grade of the liver, and a transpancreatic stealing of the portal blood flow to the shunt, as evidenced by postoperative angiography. In contrast, the reduction in PBF was minimal, that is 663 ml/min preoperatively to 562 ml/min at discharge, and 536 ml/min at late follow-up, in group B patients. Significant alterations in portal circulation of the group B patients were not evident angiographically. This US system is most useful to assess portal hemodynamics in patients with a selective shunt.     

Assessment of left-to-right atrial shunting after percutaneous mitral valvuloplasty by transesophageal color Doppler flow-mapping

To evaluate left-to-right shunts after percutaneous balloon mitral valvuloplasty, we studied 15 consecutive patients by using transesophageal color Doppler flow-imaging system. Transesophageal color Doppler examinations were performed five times in each patient (before valvuloplasty and 1 day, 1 week, 1 month, and 6 months after valvuloplasty). No shunt flow was observed before valvuloplasty. On 1 day after mitral valvuloplasty, transesophageal color Doppler echocardiography demonstrated left-to-right shunts in 13 (87%) of 15 patients. However, a significant oxygen step-up was present in the right heart in only one patient. The mean diameter of the interatrial septal defect detected by transesophageal two-dimensional echocardiography was 1.8 +/- 1.0 mm. The mean velocity of left-to-right shunting flow measured by high-pulse repetition frequency Doppler technique was 0.83 +/- 0.38 m/sec. One week after the procedure, left-to-right shunt flow was detected in 11 (73%) patients. One month after valvuloplasty, left-to-right shunting flow was detected in seven (47%) of 15 patients. There was a significant decrease in the diameter of an interatrial septal defect between 1 day and 1 week (p less than 0.01), between 1 week and 1 month (p less than 0.01), and between 1 month and 6 months (p less than 0.05). Six months after valvuloplasty, left-to-right shunting flow remained in three (20%) patients. By using transthoracic color Doppler echocardiography, we detected left-to-right shunting flow in two patients on 1 day after the procedure.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of insulin infusion on capillary blood flow in the diabetic neuropathic foot.

The effect of a short-term improvement in glycaemic control induced by insulin infusion on foot skin capillary blood flow was previously unknown. In seven Type 2 (non-insulin-dependent) diabetic subjects with neuropathy capillary blood flow was measured in the great toe nailfold by television microscopy. An estimate of arteriovenous shunt flow was obtained simultaneously in the pulp of the great toe by laser Doppler flowmetry. After omission of oral hypoglycaemic therapy for 24 h mean blood glucose was 15.7 +/- 0.7 (SEM) mmol l-1. A priming infusion of 0.1 U kg-1 of insulin was given intravenously over 15 min, followed by a variable rate insulin infusion adjusted to steadily reduce blood glucose avoiding hypoglycaemia. At the end of the study blood glucose was reduced to 6.9 +/- 0.7 mmol l-1 (p less than 0.001). During the insulin infusion, capillary blood velocity increased by 28.8% (p less than 0.05), and the diameter of the capillary erythrocyte column increased from 7.6 +/- 0.2 to 9.2 +/- 0.3 micron (p less than 0.01). Thus during the insulin infusion, the calculated capillary flow increased to 226 +/- 36% above basal values (p less than 0.01). Laser Doppler flow did not change significantly, suggesting that during insulin infusion skin blood flow is redistributed with an increase in capillary flow relative to arteriovenous shunt flow.     

Coronary artery hemodynamics in conscious dog during cardiac tamponade

We tested the hypothesis that coronary artery blood flow is sufficient to meet myocardial requirements throughout cardiac tamponade in a conscious euvolemic canine model recovered from surgery. Seven mongrel dogs were chronically instrumented to measure ascending aortic blood flow (electromagnetic flowmeter); intrapericardial, right atrial, and aortic blood pressures; regional myocardial blood flow (radionuclide labelled microspheres); and myocardial consumption of lactate, pyruvate, and oxygen. Data were collected during progressive cardiac tamponade induced by intrapericardial saline infusion to the point of hemodynamic decompensation. Decompensated cardiac tamponade (DCT) was defined as a decline in mean aortic blood pressure to 70% of the level present when the pericardial space was drained of fluid (baseline) and was produced in all animals within 25 minutes. Cardiac tamponade caused a continuous decline in coronary artery blood flow from 1.26 +/- 0.35 (baseline, mean +/- SD) to 0.53 +/- 0.15 ml/min/g (DCT, p less than 0.01), which was associated with a decrease in myocardial oxygen consumption from 1.26 +/- 0.35 (baseline) to 0.74 +/- 0.27 ml/min/g (DCT, p less than 0.05) and a slight increase in myocardial oxygen extraction from 71 +/- 3 (baseline) to 81 +/- 4% (DCT, p less than 0.05). This change in oxygen extraction occurred because of both an increase in arterial and a decrease in coronary venous oxygen content. At all degrees of cardiac tamponade, the lactate-pyruvate ratio did not change significantly from baseline (7.56 +/- 2.31), there was no evidence of lactate production, and the normal endocardial to epicardial blood flow ratio present at baseline (1.41 +/- 0.23) was preserved.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of furosemide on pulmonary shunts

In 23 mechanically ventilated anuric (six) or oliguric (17) patients (less than 16 ml/h of urine output) with severe gas exchange abnormality, we investigated the effect of furosemide on intrapulmonary shunt (Qs/QT). Before and after 0.5, 1, and 2 h of IV administration of 200 mg of furosemide, we assessed the intrapulmonary shunt and PaO2 while patients' hemodynamic measurements were monitored. Ventilatory parameters remained constant throughout the study. While the urine output was minimal and no alteration in hemodynamic values was found, the Qs/QT decreased from 27.7 +/- 2.3 percent (mean +/- SEM) at control to 24.3 +/- 2.1 percent (p less than 0.01) at 0.5 h, 21.7 +/- 2.1 percent (p less than 0.001) at 1 h, and 18.1 +/- 1.8 percent (p less than 0.001) at 2 h. The PaO2 showed no significant difference at 0.5 h but rose significantly from 96 +/- 14 to 105 +/- 14 mm Hg (p less than 0.05) and 111 +/- 14 mm Hg (p less than 0.01) at 1 and 2 h, respectively. Since we observed no changes in hemodynamics, we speculate a direct effect of furosemide in the pulmonary vasculature affecting the ventilation-perfusion mismatch and, therefore, the Qs/QT and PaO2.     

Effect of intracoronary nitroglycerin administration on phasic pattern and transmural distribution of flow during coronary artery stenosis.

BACKGROUND. Nitroglycerin is effective in relieving myocardial ischemia; however, intracoronary nitroglycerin often fails to relieve angina and has been reported to have deleterious effects on subendocardial blood flow. To understand the mechanisms involved, we evaluated the direct effect of nitroglycerin on coronary circulation of the ischemic hearts. METHODS AND RESULTS. We measured the phasic pattern of intramyocardial coronary arterial flow with an 80-channel, 20-MHz pulsed Doppler ultrasound flowmeter under moderate to severe coronary artery stenosis (distal perfusion pressure approximately 45 mm Hg group 1, n = 6) and transmyocardial blood flow distribution using radioactive microspheres while maintaining coronary pressure at a low constant level (40 mm Hg, group 2, n = 6). In anesthetized open-chest dogs, the left main coronary artery was perfused directly from the right carotid or femoral artery. In this bypass circuit, pressure was controlled with an occluder or a reservoir was connected to the circuit. In group 1, the systolic and diastolic pressures distal to the stenosis decreased significantly after intracoronary administration of nitroglycerin at maximal coronary flow from 66.5 +/- 18.5 to 56.5 +/- 13.8 mm Hg (p less than 0.01) and from 36.6 +/- 14.4 to 27.5 +/- 8.9 mm Hg (p less than 0.01), respectively. The phasic pattern of the septal artery flow was predominantly diastolic and was characterized by systolic reverse flow even in the absence of stenosis. Coronary stenosis increased systolic reverse flow. Nitroglycerin increased diastolic forward flow (p less than 0.05) but augmented systolic reverse flow markedly (p less than 0.001). In group 2, nitroglycerin increased subepicardial flow (p less than 0.05) but failed to increase subendocardial flow. With the administration of nitroglycerin, the subendocardial-to-subepicardial flow ratio decreased significantly from 0.73 +/- 0.19 to 0.32 +/- 0.14 (p less than 0.01). CONCLUSIONS. The increased systolic reverse flow after intracoronary administration of nitroglycerin may be closely related to failure of subendocardial blood flow to increase with increase subepicardial flow.     

Hemodynamic effects of glucagon in portal hypertension

It has been suggested that glucagon contributes to the pathogenesis of portal hypertension by increasing portal blood flow. This study examined this issue by assessing the hemodynamic effects of a pharmacological dose of glucagon (1 mg, intravenously) in patients with cirrhosis and portal hypertension (n = 10) and in subjects without significant liver disease (controls = n = 5). Patients with cirrhosis had much higher glucagon levels than control subjects (875 +/- 167 vs. 186 +/- 25 pg/ml, p less than 0.01) and showed blunted hemodynamic responses after glucagon administration. This occurred despite greater circulating glucagon levels, probably because of a significant prolongation of the plasma half-life of exogenously administered glucagon (4.9 +/- 0.4 vs. 2.7 +/- 0.1 min, p less than 0.1). Control subjects had marked increases in heart rate (+ 19% +/- 4%, p less than 0.01), cardiac index (+ 16% +/- 4%, p = 0.01) and arterial pressure (+ 10% +/- 3%, p less than 0.05), but corresponding changes in patients with cirrhosis (+ 7% +/- 1%, + 6% +/- 1%, and + 6% +/- 2%, respectively) were significantly less pronounced (p = 0.05), and there was a negative correlation between basal glucagon levels and the response of heart rate to glucagon injection (r = -0.804, p less than 0.001). Resistance to the systemic effects of glucagon in cirrhosis may thus be caused by a down-regulation of vascular glucagon receptors. In addition, glucagon administration caused a significant increase in portal pressure (from 18.1 +/- 1.1 to 19.0 +/- 1.2 mm Hg, p less than 0.01), as well as in azygos blood flow (from 0.54 +/- 0.03 to 0.64 +/- 0.04 L/min, + 19% +/- 4%, p less than 0.02), reflecting increased portocollateral blood flow. These findings are consistent with the hypothesis that glucagon is one of the factors contributing to the splanchnic vasodilatation and increased portal pressure of cirrhosis.     

Short-term portal hemodynamic effects of partial splenic embolization for hypersplenism

BACKGROUND/AIMS: The purpose of this study was to investigate the short-term effects of partial splenic embolization (PSE) for hypersplenism on portal hemodynamics and liver function. METHODOLOGY: Thirty-seven patients with hypersplenism were included in this study. RESULTS: The wedged hepatic venous pressure before and after PSE were 39 +/- 10 and 33 +/- 8 cmH2O, respectively, showing significant change (p < 0.01). The flow volumes of the splenic vein before and after PSE were 477 +/- 200 and 319 +/-187 mL/min, respectively, also showing significant change (p < 0.05). However, the flow volumes of the portal vein before and after PSE were 713 +/- 284 and 684 +/- 152 mL/min, respectively, showing no significant change. The blood laboratory parameters showed no significant change after PSE. PSE damaged neither the portal blood flow volume nor the liver function, although it improved the local hyperdynamic state in the splenic area and thrombocytopenia. CONCLUSIONS: In conclusion, PSE is a safe and effective treatment for hypersplenism from the portal hemodynamic point of view.     

Peripheral portosystemic shunt and its selectivity changes measured on duplex ultrasound

BACKGROUND/AIMS: Portosystemic shunts offer a symptomatic treatment for portal hypertension. Their main disadvantage is decreased perfusion of the liver with portal blood. Change of peripheral shunts into total shunts after a period of time is described. This study aims to evaluate long-term hemodynamic changes in peripheral portosystemic shunts. METHODOLOGY: The study was based on 12 patients in whom distal splenorenal shunts 8 patients) and mesocaval shunts (4 patients) were indicated respectively. Duplex sonography was used to measure the blood flow in the portal, splenic and mesenteric veins before shunt surgery and minimally 14 months postoperatively. RESULTS: It was found that the reduction of the portal blood flow was not critical and no centralization of the shunt was observed. CONCLUSIONS: Long-term blood flow in the portal vein was not severely reduced after peripheral portosystemic shunt creation, therefore the peripheral portosystemic shunt still has a role in the treatment of some patients with portal hypertension.     

Effect of portacaval shunt on drug disposition in patients with cirrhosis

To examine the consequences of liver blood flow variations on drug disposition in cirrhosis, we studied the effects of portacaval shunt on drug clearance in 35 cirrhotic patients. Lidocaine clearance and bioavailability, indocyanine green (ICG) clearance, aminopyrine breath test, and hepatic blood flow were measured before and 18 months after surgery. The patients were divided into two groups according to severity of disease: 14 patients (group 1) had slight liver dysfunction (ICG extraction ratio greater than 0.25) and 21 patients (group 2) had severe liver disease (ICG extraction ratio less than 0.25). After portacaval shunt the decrease in hepatic blood flow was similar for both groups (-65%). In group 1, ICG systemic clearance decreased from 9.10 +/- 0.68 to 4.40 +/- 0.34 ml/min . kg (p less than 0.05), whereas ICG intrinsic clearance remained unchanged; lidocaine systemic clearance decreased from 7.93 +/- 0.93 to 5.09 +/- 0.33 ml/min . kg (p less than 0.05), whereas lidocaine intrinsic clearance remained unchanged; bioavailability increased from 0.601 +/- 0.076 to 1, resulting in an abrupt reduction of oral clearance from 18.01 +/- 4.90 to 5.09 +/- 0.33 ml/min . kg (p less than 0.05). In group 2, ICG systemic clearance decreased slightly from 3.90 +/- 0.39 to 2.28 +/- 0.16 ml/min . kg (p less than 0.01) and ICG intrinsic clearance was not modified; lidocaine systemic and intrinsic clearance remained unchanged; and bioavailability increased from 0.779 +/- 0.229 to 1, resulting in a decrease of oral clearance from 7.68 +/- 1.65 to 4.23 +/- 0.37 ml/min X kg (p less than 0.05). The aminopyrine breath test was not affected by surgery in either group. We conclude that reduction of hepatic blood flow after portacaval shunt has only minimal effects on drug disposition in patients with severe liver disease, but results in a notable reduction in the clearance of high-extraction drugs in cirrhotics with mild liver disease.     

Acute hemodynamic effects of intravenous isradipine

The acute hemodynamic effects of isradipine, a new dihydropyridine calcium antagonist, were evaluated in 16 men referred for elective cardiac catheterization. Low-dose (0.007 mg/kg, n = 8) and high-dose (0.015 mg/kg, n = 8) isradipine was administered intravenously over 10 minutes and the hemodynamic alterations assessed 10 minutes after completion of infusion. Low-dose isradipine caused increases in heart rate (68 +/- 9 to 79 +/- 12 beats/min, p less than 0.001) (mean +/- standard deviation), cardiac index (3.0 +/- 0.7 to 4.1 +/- 0.9 liter/min/m2, p less than 0.001) and coronary sinus blood flow (114 +/- 27 to 162 +/- 74 ml/min, p less than 0.01), and significant decreases in mean aortic pressure (104 +/- 17 to 92 +/- 10 mm Hg, p less than 0.01), systemic and coronary vascular resistance. High-dose isradipine caused similar effects: the heart rate increased (72 +/- 6 to 84 +/- 14 beats/min, p less than 0.005), as did the cardiac index (3.0 +/- 0.6 to 4.6 +/- 0.9 liter/min/m2, p less than 0.001) and coronary sinus blood flow (122 +/- 48 to 166 +/- 47 ml/min, p less than 0.025). In addition, there were increases in the stroke volume index (43 +/- 10 to 55 +/- 8 ml/m2, p less than 0.001) and left ventricular stroke work index (69 +/- 12 to 79 +/- 12 g-m/m2, p = 0.05) after the high-dose infusion. Vascular resistance declined significantly in the systemic, pulmonary and coronary beds.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of 99mTc-teboroxime with thallium for myocardial imaging in the presence of a coronary artery stenosis

BACKGROUND. This study tested the hypotheses in the setting of a coronary artery stenosis that 1) planar 99mTc-teboroxime myocardial scans are capable of providing a good estimate of relative coronary flow reserve, and 2) delayed washout of the tracer from the myocardium is a marker of reduced myocardial blood flow and, in certain cases, myocardial ischemia. METHODS AND RESULTS. Experiments were conducted in eight closed-chest domestic swine prepared with an artificial stenosis that reduced diameter of the left anterior descending coronary artery by 80%. Measurements of hemodynamics, regional myocardial blood flow, oxygen, and lactate metabolism were made 1) at baseline, 2) after 5 minutes of intravenous infusion of adenosine and neosynephrine ("stress"), and 3) at recovery 2 hours after discontinuing the adenosine/neosynephrine infusion. Simultaneous intravenous injection of teboroxime (approximately 9 mCi) and thallium (approximately 3.5 mCi) was made at peak stress, and serial planar teboroxime imaging began 1-2 minutes later. Scans were made in dynamic mode for 30 seconds each for 7 minutes after which a stress thallium scan (7 minutes acquisition) was obtained. A redistribution thallium scan was made 2 hours later after which a repeat teboroxime injection followed by serial imaging for 7 minutes was performed. The animal was then killed, and the heart removed for determination of microsphere activity. Under baseline conditions, transmural myocardial blood flow (ml/min/g) distal to the stenosis (1.06 +/- 0.17) was reduced (p less than 0.01) compared with the normally perfused circumflex zone (1.50 +/- 0.31). In response to intravenous infusion of adenosine/neosynephrine, flow increased (p less than 0.01) compared with baseline in both distal (2.00 +/- 0.84) and circumflex (4.67 +/- 1.55) zones. However, the distal : circumflex flow declined (0.45 +/- 0.17) compared with baseline (0.73 +/- 0.17; p less than 0.01). Two hours later flow had returned to baseline levels in both zones, and lactate production during stress (-41.7 +/- 37.5 mumol/min/100 g) had reverted to consumption (13.6 +/- 7.7; p less than 0.05). Analysis of stress teboroxime scans demonstrated 1) an increase (p less than 0.01) in the ischemic : normal zone (IZ:NZ) count between 30-second (0.50 +/- 0.14) and 7-minute scans (0.61 +/- 0.11); 2) a good correlation between the 30-second scan IZ:NZ count and the stress distal : circumflex flow (0.45 +/- 0.17; r = 0.74; p less than 0.05; slope = 0.90; intercept = 0); and 3) a close correlation between the IZ:NZ count of the 7-minute scan (0.61 +/- 0.11) and the recovery distal : circumflex flow (0.69 +/- 0.21; r = 0.89; p less than 0.01). The IZ:NZ count also increased (p less than 0.01) between 30-second (0.65 +/- 0.15) and 7-minute (0.72 +/- 0.14) scans following rest injection of teboroxime. As anticipated, serial thallium scans demonstrated evidence of redistribution between stress (IZ:NZ count = 0.62 +/- 0.08) and recovery (IZ:NZ count = 0.75 +/- 0.06; p less than 0.01) time points. The stress thallium scan IZ:NZ, however, was greater than that of the 30-second teboroxime scan as well as that of the stress distal : circumflex flow. CONCLUSIONS. Accordingly, the data indicate that 1) myocardial imaging with 99mTc-teboroxime is valuable in the noninvasive assessment of relative coronary flow reserve and that 2) delayed washout of the tracer from the myocardium reflects reduced myocardial blood flow and, under conditions comparable to those of the present study, may be a marker of myocardial ischemia.     

Systemic hemodynamic and cardiac function changes in patients undergoing orthotopic liver transplantation

The objective of this study was to determine the changes in systemic hemodynamics (systemic vascular resistance [SVR], cardiac output [CO], systemic blood pressure [SBP]) and cardiac function (pulmonary artery pressure [PAP] and pulmonary wedge pressure [PWP]) during the 96 hours following orthotopic liver transplantation (OLT) and correlate these with changes in hepatic and renal function and patient outcome. The study took place in a 12-bed medical respiratory intensive care unit in a large teaching hospital. Twenty-one patients had OLT performed over a 21.5-month period (January 1988 to October 15, 1989) for end stage liver disease (ESLD) from a variety of causes. A flow-directed right heart catheter and an indwelling arterial cannula were inserted for hemodynamic monitoring over a 96-hour postoperative period. Liver and renal function studies, total serum calcium, serum albumin, and fluid balance were determined daily. The SVR increased significantly to 12.8 +/- 0.6 U at 48 hours compared with immediate (less than 8 hours) postoperative levels (p less than 0.05) and remained elevated for 96 hours. The CO fell progressively and was significantly lower than baseline values from 64 to 96 hours. There was significant inverse correlation between the increase in SVR and the fall in CO (r = .85, p less than 0.01). The SBP was stable except for a small, but significant fall at 16 and 24 hours postoperatively. The PWP increased significantly from a baseline value of 12.5 +/- 0.9 mm Hg to 15 +/- 0.9 mm Hg at 32 hours and remained elevated through 96 hours (p less than 0.05). The serum bilirubin level fell progressively postoperatively and the prothrombin time and partial thromboplastin time (PTT) shortened significantly. Bile flow increased progressively from 107 +/- 120 ml/24 hours at the end of the first 24 hours to 188 +/- 125 ml/24 hours by 96 hours postoperatively. Five patients died from nine to 43 days postoperatively. These patients' hemodynamic parameters were not significantly different from the patients who survived. Successful OLT is associated with a rapid increase in SVR and a fall in CO without changes in SBP. These findings tend to parallel the improvement found in results of liver function tests. However, there is no correlation between the improvement in the hemodynamic state and long-term survival.