Left ventricular surface tissue oxygen pressures determined by oxygen sensitive multiwire electrodes in pigs.
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Animals↗
Biomedical subjects
J Hobbhahn
Publications and source records attributed to J Hobbhahn.
Pulmonary hypertension after heparin-protamine: roles of left-sided infusion, histamine, and platelet-activating factor.
Severe pulmonary hypertension after protamine neutralization of heparin is an infrequent but life-threatening event following cardiopulmonary bypass. The effect of left ventricular infusion of protamine on pulmonary hypertension as well as a possible role of platelet-activating factor (PAF) or histamine in the heparin-protamine reaction was investigated in 30 pigs in four different groups during general anesthesia. Group 1 animals received 250 IU/kg heparin, followed by 100 mg protamine intravenously after 15 min. In group 2 protamine was infused into the left ventricle. Group 3 animals received the histamine H1- and H2-antagonists clemastine and ranitidine 5 min before protamine infusion. In group 4 the PAF receptor blocker WEB 2086 was given 5 min before protamine. Platelet-activating factor was measured by a bioassay in serum samples of group 1 and group 4 animals. In all four groups protamine caused severe pulmonary hypertension, thromboxane A2 release, and a transient decrease in leukocyte counts. No PAF release was detected after protamine infusion. Neither left ventricular infusion of protamine nor histamine or PAF antagonists prevented or attenuated the reactions after protamine infusion. The authors conclude that left ventricular infusion of protamine provides no protection from pulmonary hypertension, and that histamine and PAF are not involved in the acute pulmonary vasoconstriction after protamine neutralization of heparin.
Animals↗
Myocardial contractility, blood flow, and oxygen consumption in healthy dogs during anesthesia with isoflurane or enflurane.
Left ventricular contractility (Vmax), myocardial blood flow (MBF), and oxygen consumption (O2C) were determined together with systemic hemodynamic parameters in a total of 21 mongrel dogs. Baseline recordings were obtained under basal anesthetic conditions with a narcotic (piritramid, IV). In the control group (n = 7), recordings were obtained during a three-hour observation period with infusion of piritramid. In experimental groups measurements were repeated with equi-anesthetic concentrations of isoflurane (0.7 and 1.4 vol%; n = 8) and enflurane (1.1 and 2.2 vol%; n = 6). Dose-dependent reductions of arterial pressure, cardiac output (CO) and peripheral vascular resistance were observed with isoflurane and enflurane. CO at the higher anesthetic level was depressed significantly more with enflurane. This difference was obviously due to a more severe depression of myocardial contractility with enflurane; Vmax was decreased by 18% and 26% with enflurane, but only by 10% and 17% with isoflurane (P less than 0.01). MBF and the fraction of CO received by the heart were increased above their baseline values with both concentrations of isoflurane. In contrast, the fraction of CO remained constant with enflurane while MBF decreased. O2C was reduced due to decreases of afterload and left ventricular contractility. The reduction was greater with enflurane than with isoflurane. All parameters remained unchanged in the control group. The results of this study indicate that the most striking difference in the actions of isoflurane and enflurane on cardiac parameters is on myocardial vascular resistance; MBF is increased with isoflurane, but is decreased with enflurane although myocardial perfusion pressure is reduced by almost identical amounts.(ABSTRACT TRUNCATED AT 250 WORDS)
Analysis of Variance↗
Myocardial surface PO2--an indicator of myocardial tissue oxygenation?
The validity of myocardial surface tissue PO2 (PtO2) as a reliable indicator of transmural myocardial tissue oxygenation was studied in six anaesthetised, open chest pigs. Epicardial surface PtO2 was correlated with other variables of myocardial tissue oxygenation such as regional blood flow, coronary venous PO2, O2 saturation, PCO2 and regional myocardial lactate extraction. The study design was based on an experimental model in which the effects of a pacing induced tachycardia on tissue oxygenation of ischaemic and normally supplied myocardium were measured. Two platinum multiwire surface electrodes were placed on the epicardium, on the areas supplied by the left anterior descending coronary artery (LAD) and the left circumflex coronary artery (CX). The LAD was constricted to reduce mean surface PtO2 in the LAD area to about 50% of its baseline value. This did not affect surface PtO2 in the CX area. The reduction of surface PtO2 in the LAD area was associated with decreases in coronary venous PO2 and O2 saturation and with increases in coronary venous lactate and PCO2. Subendocardial regional blood flow and the subendocardial to subepicardial flow ratio were significantly lower than in the CX area. Increasing the heart rate by pacing (+45 beats.min-1) led to an increased degree of ischaemia as shown by fall in surface PtO2 in the LAD area to values around zero kPa, by marked increase in coronary venous lactate and PCO2, by reduction in total (-10%) and subendocardial (-40%) LAD flow and by deterioration of the subendocardial to subepicardial flow ratio. The increased degree of ischaemia was not accompanied by an increase in O2 extraction. The marked decrease in surface PtO2 occurred in spite of a slight increase in the subepicardial regional blood flow (+10%); thus the increase in O2 delivery was not sufficient to meet the increase in O2 demand. Total flow was increased by 27% in the CX area without changes in the subendocardial to subepicardial flow ratio and in the surface PtO2 values. When pacing was stopped, surface values of PtO2 in the LAD area returned to prepacing values, as did lactate extraction and coronary venous PCO2. Clear and close relationships with surface PtO2 were found for regional lactate extraction, coronary venous PCO2 and the normalised subendocardial RBF. Poor or no correlations were found for the normalised subepicardial regional blood flow, the coronary venous O2 saturation and the absolute values of subendocardial and subepicardial regional blood flow.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Regional blood flow and tissue oxygen pressures of the collateral-dependent myocardium during isoflurane anesthesia in dogs.
The authors investigated the effects of isoflurane on blood flow and tissue oxygen pressures of a collateral-dependent myocardium. Seventeen dogs divided into two groups were studied 3-4 weeks after implantation of ameroid coronary artery constrictors to completely occlude the proximal part of the left anterior descending artery. Experiments were performed during anesthesia with an opiate that was infused intravenously throughout the experiments. In Group 1 (n = 9), measurements were obtained during control and during isoflurane- (1.6-2.2 vol%) induced hypotension (mean arterial pressure, 60 mmHg). In Group 2 (n = 8), the identical protocol was applied, but norepinephrine was infused to maintain normotension. Dipyridamole effects were studied in five animals of Group 2 after a second control period at least 1 h after discontinuation of isoflurane. Isoflurane-induced hypotension caused reductions of blood flow and surface tissue oxygen pressures in the collateral flow-dependent area. Vasodilation in the normal left ventricular areas was demonstrated by an unchanged blood flow despite a reduced oxygen consumption and by a significantly increased coronary sinus hemoglobin oxygen saturation. When arterial pressure was maintained at its control level by norepinephrine, tissue oxygen pressures remained constant and collateral as well as normal area flow increased significantly during isoflurane. Coronary vascular resistance was lower during administration of isoflurane and norepinephrine compared with that during isoflurane induced hypotension, suggesting a significant contribution of tissue oxygen demand in regulation of coronary vascular resistance. At comparable levels of arterial pressure and left ventricular oxygen consumption, normal zone blood flow was significantly higher during dipyridamole than during isoflurane and norepinephrine. Thus, isoflurane-induced hypotension decreased blood flow and tissue oxygen pressures of collateral flow-dependent myocardial areas. However, neither isoflurane nor dipyridamole caused such alterations when arterial pressure was normal.
Anesthesia, Intravenous↗
[Effect of inhalation anesthetics on the myocardium].
A review of the myocardial effects of the volatile anesthetics halothane (HAL), enflurane (ENF) and isoflurane (ISO) is presented. In the first part the effects on cardiac rhythm, myocardial contractility and oxygen supply are discussed. In the second part the pathophysiology of myocardial ischemia during anesthesia and surgery is summarized. Finally the role of inhalation anesthetics in inducing or preventing myocardial ischemia is considered, with special regard to the "coronary steal" phenomenon.
Anesthesia, Inhalation↗
Thromboxane mediation of pulmonary hemodynamic responses after neutralization of heparin by protamine in pigs.
Protamine neutralization of heparin is often associated with severe hemodynamic side-effects, including pulmonary hypertension and systemic hypotension. Because prostanoids may be involved, the authors studied the role of arachidonic acid metabolites, especially thromboxane A2, in this process. During anesthesia with enflurane and fentanyl, four groups of pigs were studied: Group 1 (n = 10) received heparin (250 IU/kg), followed by protamine (100 mg) after 15 minutes to neutralize the heparin. The same protocol was used in group 2 (n = 11), except that the thromboxane A2 receptor antagonist BM 13.177 (10 mg/kg) was infused 5 minutes before the protamine. The protocol for group 1 was also used for group 3 (n = 7) except that these animals were pretreated with indomethacin (10 mg/kg). Animals in group 4 (n = 10) were given protamine only (100 mg). Pulmonary artery pressure and pulmonary vascular resistance increased significantly in group 1 after protamine neutralization of heparin. This was accompanied by significant increases in plasma concentrations of the cyclooxygenase products thromboxane B2, 6-keto-prostaglandin F1 alpha, and prostaglandin F2 alpha. Cyclooxygenase products increased to comparable degrees in group 2, but without hemodynamic effects. Leukocyte counts decreased comparably in both groups. Hemodynamic reactions, as well as changes in plasma prostanoid levels were absent in group 3, and group 4, but leukocyte counts were less affected in animals that received protamine alone. The results indicate that the hemodynamic side-effects of protamine are mediated by prostanoids and that thromboxane A2 release is the pivotal step, because side effects were effectively prevented by pretreatment with a thromboxane receptor antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Left ventricular oxygen tensions in dogs during coronary vasodilation by enflurane, isoflurane and dipyridamole.
The purpose of this study was to investigate the effects of the anesthetics enflurane and isoflurane and of the coronary vasodilator dipyridamole on myocardial oxygen balance and myocardial tissue oxygen tensions. The studies were performed in 24 open-chest dogs during basal anesthesia with a narcotic. Myocardial blood flow (MBF) was measured using radioactive microspheres, myocardial surface tissue PO2 by means of a platinum multiwire surface electrode. One control group and three experimental groups were studied: enflurane (1.1 vol%), isoflurane (0.7 vol%, both end-tidal concentrations), and dipyridamole (0.4 mg/kg). Mean arterial pressure significantly decreased to an average of 70 mm Hg in all three experimental groups. Although MBF was unchanged during enflurane (-18%) and isoflurane (+20%), it increased during dipyridamole (+304% p less than 0.05 vs baseline and control, enflurane, and isoflurane groups). Myocardial oxygen consumption decreased significantly during enflurane and isoflurane but remained unchanged during dipyridamole. Thus, the ratio between myocardial oxygen delivery and consumption increased 6% with enflurane (p less than 0.05 vs baseline), 47% with isoflurane (p less than 0.05 vs baseline and control group) and 280% with dipyridamole (p less than 0.05 vs baseline and control, enflurane, and isoflurane groups). Coronary venous PO2 remained unchanged during enflurane but increased significantly during isoflurane and dipyridamole. Left ventricular surface tissue PO2 was unchanged in enflurane and isoflurane animals and decreased slightly, yet significantly, during dipyridamole. All variables remained unchanged in the control group. Thus, isoflurane and dipyridamole interfered with MBF autoregulation and increased myocardial oxygen delivery out of proportion to myocardial demands.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Splanchnic oxygen consumption and hepatic surface oxygen tensions during isoflurane anesthesia.
Blood flow to and oxygen consumption of the splanchnic organs were determined together with hepatic surface oxygen tensions in 18 mongrel dogs anesthetized with the long-acting narcotic piritramid. Twelve animals also received 0.7 Vol% and 1.4 Vol% isoflurane; six time-related controls received piritramid only. Surgical preparation consisted of a left thoracotomy for inserting a catheter into the left atrium for microsphere injections and for gaining access to the hepatic surface through an incision in the diaphragm. Parameters in the animals receiving isoflurane were recorded at three stages: stage 1--piritramid anesthesia after surgical preparation; stage 2-60 min after addition of 0.7 Vol% (end-expiratory) isoflurane; stage 3-60 min after addition of 1.4 Vol% (end-expiratory) isoflurane. Hepatic surface oxygen tension was determined at each stage using an eight-channel oxygen sensitive electrode. Mean arterial pressure and cardiac output decreased during both stages with isoflurane; hepatic arterial inflow remained constant. Portal blood flow and, hence, total hepatic inflow decreased significantly. An unchanged splanchnic O2 consumption induced lower hepatic venous pO2 values: 40 +/- 1 mmHg at control, 35 +/- 2 mmHg, and 31 +/- 2 mmHg (mean +/- SEM; both P less than 0.05) during isoflurane. A concomitant decrease of hepatic surface pO2 values indicated an altered tissue oxygenation. The percentage of hepatic surface pO2 values in the lowest pO2 range (0-5 mmHg) increased significantly from 8.4 to 20.3% during 1.4 Vol% isoflurane; the percentage of values of 0 mmHg increased from 2.4 to 9.8% during 1.4 Vol.%. No changes of these parameters were detected in the control animals during the 3-h observation period.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Beneficial effect of cyclooxygenase inhibition on adverse hemodynamic responses after protamine.
The hypothesis that adverse effects observed when heparin is antagonized by protamine are mediated by metabolites of the arachidonic acid cascade was tested during general anesthesia (enflurane, fentanyl) in 16 pigs classified into two groups. In the first group (n = 9), effects of intravenously administered protamine on systemic hemodynamics, blood/gas tensions, and arterial and mixed-venous prostanoid levels were studied. The second group (n = 7) was pretreated with indomethacin 10 mg/kg, and the same measurements were made. All pigs received heparin 150 units/kg. When protamine 1.1 +/- 0.1 mg/kg was administered over 3 minutes, marked hemodynamic alterations were observed in group 1: pulmonary artery pressure and pulmonary vascular resistance increased, and left ventricular end-diastolic and systemic arterial pressures decreased. Arterial and mixed-venous PO2 values deteriorated in all pigs in group 1 at the end of protamine infusion. These alterations were accompanied by significantly elevated prostanoid levels in arterial and mixed-venous plasma samples: Thromboxane A2, prostaglandin F2 alpha, KH2-PGF2 alpha (a metabolite of prostaglandin F2 alpha), and prostacyclin were maximally elevated at completion of protamine and remained significantly above control values at 5 minutes but were not significantly different from control after 10 minutes. Blocking the cyclooxygenase cascade by pretreatment of the pigs with indomethacin (group 2) prevented hemodynamic and blood gas alterations. It is concluded that in pigs the detrimental side effects associated with the use of protamine to reverse heparin are mediated by metabolites of the cyclooxygenase cascade.(ABSTRACT TRUNCATED AT 250 WORDS)
Anesthesia, General↗
[Liver perfusion and oxygenation with isoflurane].
The influence of 0.7, 1.4 or 2.1 vol % isoflurane on hepatic blood flow and hepatic tissue oxygenation was studied in 12 dogs under basal anaesthesia with i.v. piritramid. Blood flow was measured by the microsphere method (phi = 15 micron). Tissue pO2 was determined by a platinum multiwire electrode and by measuring hepatic venous pO2. Isoflurane effected a marked fall in arterial blood pressure in these surgically not stimulated animals. However, cardiac output fell only moderately due to a considerable reduction in systemic vascular resistance. Both local tissue pO2 and venous pO2 were decreased with isoflurane. A potentially hazardous reduction in hepatic tissue pO2 was found predominantly with high isoflurane concentrations. The decrease in hepatic tissue pO2 results from disadvantageous effects on hepatic O2-balance: total hepatic blood flow decreases, whereas splanchnic O2 consumption increases. The lower blood flow is due to a reduction of portal blood flow whereas arterial perfusion remains unchanged. The increase in splanchnic O2 consumption possibly results from an elevated O2 consumption of the liver. Further studies have to clarify whether the disadvantageous effects of high isoflurane concentrations fail to appear when pain-induced stimulation of the sympathico-adrenergic system counteracts the fall in arterial blood pressure.
Animals↗
Hemodynamics and oxygen transport after partial and total blood exchange with pyridoxalated polyhemoglobin in dogs.
The effects of a pyridoxalated polyhemoglobin solution (SFH-PLP)n-solution) on cardiovascular hemodynamics and oxygen transport were investigated in a model of partial and total blood exchange in seven dogs. Cardiac output, mean arterial pressure and heart rate were essentially unchanged, even after total blood exchange, due to the long plasma half-disappearance time of (SFH-PLP)n (36 h) and due to the addition of albumin to the solution. The oxygen-binding capacity of (SFH-PLP)n was 1.1 to 1.2 ml O2/g hb. Oxygen availability was reduced to about 50%, resulting from the low hemoglobin concentration and the decreased oxygen-binding capacity of (SFH-PLP)n. Since cardiac output did not increase, O2-consumption was maintained by an increase in O2-extraction from 21 to about 50%. However the decrease in mixed venous PO2 to values not below 30 mmHg (4.00 kPa) proves the sufficient unloading capacity of (SFH-PLP)n. The adequate tissue oxygenation of (SFH-PLP)n could be demonstrated by the lack of a metabolic acidosis, the essentially unchanged PO2-histograms of the skeletal muscle and the only moderate decrease in mixed venous PO2. Four dogs survived for more than 3 days; three of them were long-term survivors. This suggests that oxygen supply was maintained by (SFH-PLP)n until red blood cells were restored.
Animals↗
[Animal experiment studies on hemodynamics following partial and total blood exchange with a pyridoxalated polyhemoglobin solution].
The effects of a pyridoxalated polyhaemoglobin (SFH-PLP)n-solution on haemodynamics were investigated in a model of partial (hct = 12%) and total blood exchange (hct less than 1%) in 7 dogs. Partial blood exchange resulted in a slight increase in right atrial pressure (RAP) and pulmonary capillary wedge pressure (PCWP) and in a marked decrease in heart rate (HR). Cardiac output (CO) did not increase as would be expected from haemodilution. After total blood exchange, arterial pressure, HR, RAP, PCWP and CO were unchanged compared to the pre-exchange values during the 90 minutes of observation. However, pronounced pulmonary vasoconstriction was observed in 4 dogs. The beneficial effects on haemodynamics are due to the long intravascular persistance of the polymerized haemoglobin molecules (plasma half-disappearance time = 36 hours) and the addition of albumin supplying a sufficient colloid-osmotic pressure of the solution. These characteristics and the good oxygen unloading capacity of the pyridoxalated polyhaemoglobin resulted in longterm survival of three dogs. These results demonstrate a better haemodynamic efficacy of the (SFH-PLP)n-solution compared to previous investigations with unmodified haemoglobin solutions. However, there are still many problems, which have to be clarified prior to its clinical application.
Animals↗
Oxygen-transporting fluids and oxygen delivery with hemodilution.
The hemodynamic effectiveness and the oxygen characteristics of stroma-free hemoglobin (SFH) solutions were studied in 11 dogs. the animals were bled two-thirds of the estimated blood volume or until cardiac arrest. The shed blood was immediately replaced by equivalent amounts of either SFH or polyhemoglobin (SFH-PLP). Sixty min later, Ringer's lactate was given iv for 180 min to maintain right atrial pressure at the initial value. In a second set of experiments, the intravascular persistence of SFH-PLP was investigated in 5 dogs by withdrawal of blood (7 ml/kg bw) and immediate replacement with 131I-labeled SFH-PLP. Hemodynamic disorders after severe blood loss could be reversed by infusion of hemoglobin solutions. Due to the short intravascular persistence, cardiac output did not increase as one would expect from the degree of hemodilution. Pyridoxalation of the hemoglobin molecule reduced oxygen affinity and improved oxygen unloading at the tissue level. The short intravascular half-time of this compound could be overcome by crosslinking of the pyridoxalated hemoglobin molecules. Further studies must prove whether this polyhemoglobin can be used as a long-term oxygen-carrying blood substitute.
Animals↗
Tissue PO2 during reanimation with hemoglobin solutions.
Solutions of conventional stoma-free hemoglobin (SFH) and of pyridoxylated stoma-free hemoglobin (SFH-PLP) were compared in a dog model of reanimation from severe arterial blood loss. SFH and SFH-PLP restored central hemodynamics after infusion without yielding significant differences between the experimental groups. To cope with the developing hypovolemia, Ringer's lactate load amounted to about 120 ml/kg, edema formation was not encountered. Skeletal muscle oxygenation was studied by means of a multiwire platin electrode. The infusion of SFH-PLP was associated with a shift to the right of the cumulative PO2-distribution curve, indicating better tissue oxygenation. Oxygen was not unloaded from SFH in plasma unless the oxygen extraction from red cell hemoglobin exceeded 40%. Oxygen unloading was, however, improved when SFH-PLP with low oxygen affinity was used. Thus, SFH-PLP merits further consideration as a short-term oxygen-carrying blood substitute.
Animals↗
Myocardial oxygenation and transmural lactate metabolism during experimental acute coronary stenosis in pigs.
Measurement of surface tissue pO2 (ptO2) with surface electrodes is increasingly applied in experimental medicine. Its use on the beating heart may seem to be problematic because transmural gradients of tissue pO2 would reduce the validity of pO2 determinations in the epicardial layers. This study attempted to determine whether ptO2 may be a valid and sensitive indicator of transmural myocardial oxygenation. In order to measure ptO2, two eight-channel Clark-type electrodes were placed on a beating porcine left ventricle (n = 13). Measurements were made at different degrees of acute stenosis of the left anterior descending artery (LAD). A 24-F cannula was inserted into the great cardiac vein, draining the poststenotic myocardium to obtain coronary venous blood samples. Transmural metabolic changes were detected simultaneously by coronary venous blood gas parameters and lactate levels. Epicardial tissue pO2 was 49 +/- 2 mm Hg (mean +/- SEM) before stenosis and decreased to a mean value of 25 +/- 2 mm Hg during stenosis. Different degrees of LAD stenosis (ptO2 range: 12-35 mm Hg) were substantial enough to alter arterio-coronary venous lactate difference (avd lactate) from +0.31 +/- 0.07 mmol/l (control) to -0.62 +/- 0.15 mmol/l (stenosis). A significant linear correlation between changes of ptO2 (delta ptO2) and changes of avd lactate (delta avd lactate) resulted (y = 0.59 + 0.62x; r = 0.86; p less than or equal to 0.001). However, linear regression analysis between delta ptO2 correlated with the corresponding data from coronary venous pO2 (delta pO2cv) oxygen content (delta O2contcv), and oxygen saturation (delta O2satcv) showed no significant correlations. We conclude that measurement of ptO2 is a sensitive and valuable indicator of transmural oxygenation in ischemic myocardium, whereas pO2cv, O2contcv and O2satcv do not seem to be valid predictors of ischemia in myocardial oxygenation.
Acute Disease↗