Differential effects of acute endotoxin shock on myocardial contractility and performance.
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Animals↗
Biomedical subjects
R M Raymond
Publications and source records attributed to R M Raymond.
Hemodynamic effects of contrast media during coronary angiography: a comparison of three nonionic agents to Hypaque-76.
Coronary angiography with standard ionic contrast media is associated with marked alterations in cardiac hemodynamics because of the depressant effects of the contrast media on cardiac contractility. Nonionic contrast media have been reported to produce less hemodynamic alteration than standard ionic contrast media. However, there is no information on how one nonionic media compares to another. Thus we compared the hemodynamic effects of three nonionic contrast media, Iopamidol (IOP), Iohexol (IOH), and Ioversol (IOV) to each other as well as to the standard ionic contrast media Hypaque-76 (H76). In 20 closed-chest anesthetized dogs, we recorded the maximal change in left ventricular systolic pressure (LVSP), mean aortic pressure, left ventricular diastolic pressure (LVDP), and left ventricular dp/dt during 10-cc left main coronary artery injections of H76, IOP, IOH, and IOV. The mean aortic pressure and LVSP decreased 36 +/- 17 mm Hg and 46 +/- 21 mm Hg with H76 but only 5 +/- 5 mm Hg and 6 +/- 5 mm Hg with IOP, 5 +/- 4 mm Hg and 6 +/- 6 mm Hg with IOH, and 5 +/- 4 mm Hg and 7 +/- 6 mm Hg with IOV (P less than 0.001). The LVDP increased 6 +/- 5.0 mm Hg with H76 but only 0.2 +/- 0.5 mm Hg with IOP, 0.2 +/- 0.3 mm Hg with IOH, and 0.5 +/- 1.0 mm Hg with IOV (P less than 0.001). The LV dp/dt decreased 545 +/- 261 mm Hg/sec with H76 but increased 886 +/- 477 mm Hg/sec with IOP, 910 +/- 96 mm Hg/sec with IOH, and 473 +/- 335 mm Hg/sec with IOV (P less than 0.001). Whereas each nonionic agent produced significantly less hemodynamic abnormalities than H76, there was no significant difference between any of the nonionic agents on any hemodynamic parameter. Thus, as compared to H76, these nonionic contrast media produced only trivial alterations in hemodynamics and LV dp/dt. These agents may be preferable in patients with LV dysfunction.
Angiography↗
Effect of insulin on myocardial contractility during canine endotoxin shock.
During endotoxin shock the heart becomes less responsive to the stimulatory effect of insulin on glucose uptake. In the present study we sought to determine if the heart was also less responsive to the positive inotropic effect of insulin during non-cardiogenic endotoxin shock. Responses of the heart to insulin were assessed under conditions of hyperinsulinaemic (4U.min-1), euglycaemic clamp (INS). Adult mongrel dogs, weighing 20-25 kg, were anaesthetised and instrumented to measure differences in substrate concentrations between arterial and coronary sinus blood, circumflex artery blood flow (using electromagnetic flow probe), haemodynamic variables, and left ventricular posterior wall thickness (using sonomicrometry). The first derivative of left ventricular pressure with respect to time was measured and its maximal value (LV dP/dtmax) used as an index of cardiac performance. Myocardial contractility was measured using the end systolic pressure-dimension relationship. Endotoxin shock was induced by Salmonella typhimurium (1 mg.kg-1 intravenously), and resulted in depression of myocardial performance but increased contractility. INS caused a twofold elevation in myocardial glucose uptake in control animals while in endotoxin shocked dogs it was unable to elevate glucose uptake above the pre-endotoxin level. In control animals INS caused both increased cardiac contractility and performance. In the endotoxin shock group INS was unable to increase LVdP/dtmax above the basal, pre-endotoxin level and did not cause any significant change in myocardial contractility. We suggest that the heart becomes less responsive to the positive inotropic as well as metabolic effects of insulin during endotoxin shock. Changes in LV dP/dtmax can be attributed to the changing loading conditions that occur during endotoxin shock.
Animals↗
Contrast media-induced ventricular fibrillation. A comparison of Hypaque-76, Hexabrix, and Omnipaque.
Contrast media occasionally produce ventricular fibrillation during coronary angiography. We compared the fibrillatory propensity of the conventional ionic contrast medium, Hypaque-76 (H76) to the low osmolar ionic dimer Hexabrix (HB) and to the nonionic agent Omnipaque (OM) in 20 open chest anesthetized dogs. Intracoronary injection of 6 mL of contrast medium produced spontaneous ventricular fibrillation in four of ten dogs with H76, compared with two of ten with HB, and zero of ten with OM (P = .07). The induction of two premature beats by programmed stimulation of the myocardium during injection of 4 mL of contrast medium produced ventricular fibrillation in ten of ten dogs with H76, compared with three of ten with HB, and zero of ten with OM (P less than .001). Both H76 and HB produced ventricular fibrillation in ten of ten dogs when three premature beats were induced, compared with two of ten dogs with OM (P less than .001). Four mL H76 produced a 109 +/- 18 msec increase in the QT interval, compared with an 82 +/- 17 msec increase with HB, and a 45 +/- 12 msec increase with OM. We conclude that both low osmolar HB and OM are less fibrillatory than the conventional ionic medium H76, and that the nonionic medium OM is less fibrillatory than the ionic dimer contrast medium HB.
Angiography↗
Effects of contrast media on the conducting system of the heart during coronary angiography. A comparison of Renografin-76 to Hypaque-76.
Electrocardiographic changes induced by ionic contrast media can cause complications during coronary angiography. A conduction delay through various parts of the heart is one factor in the genesis of asystole or ventricular fibrillation. Hypaque-76 (H76) and Renografin-76 (R76) are nearly identical ionic contrast media except that R76 binds more calcium than H76 because of the presence of sodium citrate and EDTA in R76. To determine whether the calcium binding additives in ionic contrast media contribute to the cardiac conduction abnormalities, we examined conduction time through the atrioventricular (AV) nodal tissue (via bipolar His bundle electrograms) and through the distal part of the conduction system (recording the QRS complex from the ECG) during coronary angiography. We injected 10 mL of H76 and R76 in 19 closed chest dogs in a blinded, randomized fashion during coronary angiography. The effects of H76 and R76 on heart rate, AH interval, HV interval, V interval and PR interval, and QRS complex duration were recorded. In 14 nonatrial pacing dogs, compared with H76, R76 produced a greater increase in the AV interval (32.9 +/- 6 milliseconds vs 12.4 +/- 2 milliseconds, P less than .01) and the PR interval (29.6 +/- 6 milliseconds vs 11.9 +/- 4 milliseconds, P less than .02). Additionally, the heart rate decreased 13.9 +/- 3.5 beats/minute from control with R76 compared with a decrease of 4.2 +/- 2.6 beats/minute from control with H76 (P less than .05). There was no significant difference between the prolongation of the HV interval and V interval, or QRS complex duration generated by R76 and H76.(ABSTRACT TRUNCATED AT 250 WORDS)
Angiography↗
Adenosine potentiates insulin-stimulated myocardial glucose uptake in vivo.
Myocardial adenosine (ADO) has long been regarded as a regulator of coronary blood flow. In other tissues, such as adipose and skeletal muscle, much attention has focused on the role of ADO as a metabolic regulator of the actions of insulin. In the present study, we determined the effect of ADO infusion on insulin-stimulated myocardial glucose uptake (MGU). Mongrel dogs of either sex were instrumented to obtain arterial-coronary sinus differences for glucose, lactate, and oxygen. These were multiplied by circumflex artery blood flow (Q) to obtain uptake values. Measurements were made before and during hyperinsulinemic (4 U/min)-euglycemic clamp (clamp) with intracoronary infusions of saline, ADO, adenosine deaminase (ADA), or nitroprusside (NP). During clamp, MGU increased from a basal value of 3.0 +/- 0.8 mg/min (mean +/- SE) to 5.53 +/- 0.8 mg/min. Adenosine infusion potentiated this response, raising MGU further to 9.02 +/- 1.1 mg/min while not significantly affecting lactate or oxygen uptakes. Infusion of ADA confirmed the specificity of the response by blocking the metabolic effect of exogenously infused ADO. When NP was infused, Q increased significantly without altering MGU, indicating that the metabolic response to ADO was independent of the changes it caused in Q. A dose-response relationship existed between ADO and insulin-stimulated MGU. The metabolic response to ADO was more sensitive than the vasodilator response. It is concluded that ADO acts as a regulator of insulin in heart. This metabolic regulation occurs independent of changes in coronary blood flow.
Adenosine↗
Myocardial insulin resistance during acute endotoxin shock in dogs.
Myocardial insulin responsiveness was determined in open-chest pentobarbital sodium-anesthetized dogs before and after endotoxin administration. Animals were instrumented to measure mean arterial blood pressure (MABP), heart rate (HR), and coronary blood flow. Myocardial glucose uptake and myocardial oxygen uptake (MVO2) were determined during a basal control period and after a hyperinsulinemic-euglycemic clamp procedure over a wide range of insulin concentrations. The clamp was accomplished by intravenously infusing insulin (0-4000 mU/min) and 20% glucose in sufficient amounts to maintain arterial glucose concentrations within 5 mg/dl of the control value. In a separate series of experiments, myocardial insulin responsiveness was determined by use of a single dose of insulin (4000 mU/min). This was done to determine whether antecedent insulin infusions during the sequential clamp procedure would affect the responsiveness of the heart. In control experiments, myocardial glucose uptake increased without any changes in HR, MVO2, or MABP. Maximum myocardial glucose uptake occurred at an insulin infusion rate between 400 and 4000 mU/min. A single concentration of insulin resulted in similar increases in myocardial glucose uptake as with the sequential clamp protocol. Acute endotoxin shock was induced by bolus injection of 1 mg/kg Salmonella typhimurium endotoxin (Difco Labs, Detroit, MI). One hour after administration of endotoxin, basal myocardial glucose uptake was decreased compared with the control animals. After 1 h of endotoxin shock, the heart was refractory to all concentrations of insulin, suggesting the site for altered insulin response was being mediated by a postreceptor mechanism.
Animals↗
Adenosine is required for myocardial insulin responsiveness in vivo.
The adenosine-receptor antagonist 8-phenyltheophylline (8-PTH) was used to study the role of endogenous adenosine in modulating insulin-stimulated myocardial glucose uptake (MGU) in vivo. Dogs were surgically instrumented under pentobarbital sodium anesthesia to measure hemodynamics and obtain blood samples for determinations of oxygen and glucose concentrations. Myocardial uptake of these substances was calculated as the product of the appropriate arterial-coronary sinus differences and circumflex blood flow. The response to insulin was determined with the hyperinsulinemic-euglycemic clamp technique. During insulin infusion, MGU increased from 3.12 +/- 0.8 to 9.20 +/- 1.8 mg/min (mean +/- SE). In contrast, insulin failed to increase MGU when 8-PTH was being infused into the circumflex artery. These results demonstrate that some degree of adenosine-receptor-mediated activity is required for insulin to stimulate myocardial glucose uptake. It is suggested that the presence of adenosine at its receptor may be an important factor during conditions in which myocardial insulin resistance may develop.
Adenosine↗
Sodium effects on the fibrillatory propensity of non-ionic contrast media.
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Animals↗
Coronary angiography during acute myocardial infarction in dogs. A comparison of the hemodynamic effects of ionic and nonionic contrast media.
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Animals↗
Coronary angiography during acute myocardial infarction in dogs: comparison of the hemodynamic effects of ionic and nonionic contrast media.
We compared the hemodynamic effects during coronary angiography of three nonionic contrast media, iopamidol, iohexol, and ioversol, with each other as well as with the standard ionic contrast medium containing 66% diatrizoate meglumine and 10% diatrizoate sodium (Hypaque-76) in the presence of a left anterior descending coronary artery occlusion in dogs. In 13 opened-chest anesthetized dogs, we recorded the maximal change in left ventricular systolic pressure (LVSP), mean aortic pressure (MAP), left ventricular diastolic pressure (LVDP) and rate of rise in left ventricular pressure (LV dp/dt) during left main coronary artery injections of 10 ml each of Hypaque-76, iopamidol, iohexol, and loversal 1 hour after left anterior descending coronary artery occlusion. The changes in LVSP and MAP were, respectively, -29 +/- 12 mm Hg and -21 +/- 11 mm Hg with Hypaque-76, 3 +/- 6.6 mm Hg and -0.2 +/- 3.6 mm Hg with iopamidol, 4.8 +/- 8.6 mm Hg and 0.5 +/- 4 mm Hg with iohexol, and -0.8 +/- 6 mm Hg and -1.5 +/- 33 mm Hg with ioversal (p less than 0.001). The change in LVDP was 5.4 +/- 4.4 mm Hg with Hypaque-76 but -1.5 +/- 3.1 mm Hg with iopamidol, -1.7 +/- 2.4 mm Hg with iohexol, and -0.5 +/- 2.5 mm Hg with ioversol (p less than 0.001). The LV dp/dt decreased 682 +/- 318 mm Hg/sec with Hypaque-76, but increased 412 +/- 297 mm Hg/sec with iopamidol, 350 +/- 214 mm Hg/sec with iohexol, and 293 +/- 191 mm Hg/sec with ioversol (p less than 0.001). Thus, each nonionic agent produced significantly fewer hemodynamic abnormalities than Hypaque-76. There was no significant difference between any of the nonionic agents on any hemodynamic parameter. These agents may be preferable in patients with acute myocardial infarction or significantly impaired myocardial function.
Acute Disease↗
Arterial regeneration over polydioxanone prostheses in the rabbit.
We analyzed histologic, ultrastructural, and functional characteristics of rabbit aortic conduits regenerated over absorbable polydioxanone prostheses. Twenty-eight polydioxanone-elicited prosthesis/tissue complexes harvested two weeks to 12 months following implantation were analyzed grossly; photographed; sectioned for light, scanning, and transmission electron microscopy; and studied for compliance, bursting strength, and prostacyclin and thromboxane metabolite contents. No aortic-related deaths or hemorrhages occurred. Smooth regenerated conduits without stenoses were seen in 27 of 28 specimens, with one small aneurysm. Transprosthetic myofibroblast migration and proliferation paralleled the kinetics of macrophage-mediated prosthetic dissolution, which was consequently delayed compared with polyglycolic acid prostheses. Confluent endothelial-like luminal surfaces were present after two weeks. Progressive inner capsular thickening ended after three months at 420 micron. Ex vivo compliance curves resembled arterial elasticity. Regenerated tissue withstood 1200 mm Hg of systolic pressure, and 6-keto-prostaglandin F1 alpha to thromboxane B2 ratios did not differ from normal control specimens.
6-Ketoprostaglandin F1 alpha↗
Compound polyglactin 910/polypropylene small vessel prostheses.
This study evaluated morphologic and functional characteristics of tissue reactions to compound prostheses of 69% absorbable polyglactin 910 (PG910) and 31% nonabsorbable polypropylene in the rabbit. Forty-two woven PG910/polypropylene prostheses (24 X 4 mm internal diameter) implanted into rabbit infrarenal aortas were harvested after 2 weeks to 12 months. Each explant was photographed and sectioned for light microscopy and transmission and scanning electron microscopy. Randomly selected explants underwent either compliance and bursting strength measurements or assays of production of prostacyclin and thromboxane metabolites by luminal surfaces of both regenerated conduits and normal control aortas in response to administered sodium arachidonate. Results showed 100% patency with no aneurysms and 2% stenoses (1 of 42 prostheses). Confluent endothelial-like cellular luminal surfaces covering oriented smooth muscle-like myofibroblasts comprised the inner capsules whose thicknesses stabilized at 1 to 2 months. Only residual polypropylene remained in the prostheses after 2 months. Compliance studies reflected a 0.65 mm (14%) change over a pressure range of 0 to 160 mm Hg. All regenerated prosthesis-tissue complexes had bursting strengths greater than the proximal perianastomotic native aortas, which burst between 600 and 2000 mm Hg. At 1 month the rate of production of 6-keto-PGF1 alpha per square millimeter of surface area of experimental segments was normal. Production of 6-keto-PGF1 alpha by experimental segments at 3 months had increased fourfold whereas thromboxane B2 (TxB2) production remained unchanged. The 6-keto-PGF1 alpha/TxB2 ratio increased from 1 to 4 months. This study demonstrates clinically efficacious morphologic, mechanical, and biochemical characteristics of PG910/polypropylene-elicited vascular prosthesis-tissue complexes.
6-Ketoprostaglandin F1 alpha↗
The effect of sodium on the fibrillatory propensity of nonionic contrast media.
Removing sodium from standard ionic contrast media markedly increases the incidence of ventricular fibrillation in patients undergoing coronary angiography. Newer nonionic contrast media, iopamidol, iohexol, and ioversol contain only trace amounts of sodium. To determine whether sodium attenuates or potentiates ventricular fibrillation from nonionic contrast media, we measured the prolongation in QT interval and performed programmed electrical stimulation with one, two and three extra ventricular stimuli in 40 dogs during 4-mL intracoronary injections of iopamidol, iohexol, and ioversol. Solutions of each contrast medium with added NaCl at concentrations of 0.225%, 0.45%, and 0.9% were compared with standard contrast media. The addition of NaCl markedly increased the amount of QT interval prolongation produced by each contrast medium. With iopamidol, the amount of QT interval prolongation was 40 +/- 11 msec with standard iopamidol, but was 58 +/- 11 msec with 0.225% NaCl/iopamidol, 84 +/- 17 msec with 0.45% NaCl/iopamidol, and 132 +/- 42 msec with 0.9% NaCl/iopamidol (P less than .001). Similar results were seen with iohexol and ioversol. Ventricular fibrillation was difficult to induce with standard solutions of these agents (even with three extra stimuli), but became progressively easier to induce when NaCl was added. Three extra stimuli produced ventricular fibrillation in zero of 11 dogs with standard iopamidol, zero of 11 with 0.225% NaCl/iopamidol, three of 11 with 0.45% NaCl/iopamidol, and eight of 11 with 0.9% NaCl/iopamidol (P less than .001). Similar results were observed with iohexol and ioversol. The addition of choline chloride or dextrose did not increase ventricular fibrillation and QT interval prolongation. It is concluded that standard preparations of nonionic contrast media have a very low fibrillatory propensity.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Increased inotropic state during splanchnic artery occlusion shock in the dog.
Myocardial function during various forms of shock and its assessment remain the subjects of continuing controversy. Dogs were instrumented for the measurement of a lead II ECG, systemic arterial pressure, LV pressure, LVdP/dt, and LV anterior wall thickness. Afterload was varied with a snare occluder around the aorta. Contractility was assessed by the end-systolic pressure-wall thickness relationship. After taking control measurements, shock was induced by occluding the celiac and the superior and inferior mesenteric arteries for 2 hr followed by reperfusion. The end-systolic pressure-wall thickness relationship was determined at 1 and 2 hr postocclusion and then at 15, 30, 45, and 60 min postrelease and hourly thereafter. The slope of this relationship was either unchanged or increased (ie greater negative slope) during occlusion. Over the first hour of reperfusion of the splanchnic bed the slope averaged 204 +/- 17% of control, and it reached 221 +/- 41% of control by 3 hr postrelease. Myocardial depression was seen only as an agonal event (39 +/- 6% of control). Sham control dogs were stable over a 4 hr period following sham occlusion. Thus, myocardial contractility was increased during splanchnic artery occlusion shock except as a terminal event. Early depression of circulatory performance was a result of decreased venous return and not cardiac dysfunction.
Animals↗
The cerebral circulatory response during canine anaphylactic shock.
Radiolabeled microspheres were employed to measure the cerebrovascular response to severe anaphylactic-induced hypotension in pentobarbital-anesthetized dogs. A rapid drop in mean arterial pressure (MAP, 140 to below 50 mm Hg) coincided with total and regional cerebral blood flows (CBF) that were not significantly different from prechallenge values. While blood flow to the occipital region (highest measured region of the brain) was significantly greater than that of brainstem regions prior to and during the shock regimen, no major redistributional phenomena occurred to any cerebral region. These findings were in contrast with other reports that demonstrated a loss in CBF and a redistribution of regional CBF as perfusion pressures declined below 55 to 60 mm Hg. To investigate whether the maintenance of CBF during severe anaphylactic hypotension was associated with cerebral hypoxia or hypercapnia, we employed in a second group of dogs the technique of venous drainage from the confluens sinus, so that the cerebral arterial-venous difference for blood gases and other blood components could be determined. Similar to our previous findings, CBF was maintained to perfusion pressures of 39 +/- 4 mm Hg. The drop in cerebral vascular resistance during the severe hypotensive period was not associated with a significant decline in arterial PO2, or a significant increase in arterial PCO2, A-V PO2, or V-A PCO2. Our results suggest that the fall in cerebral vascular resistance during anaphylactic-induced hypotension would not be associated with a severely altered cerebral metabolism.
Anaphylaxis↗
Myocardial depression during acute pancreatitis: fact or fiction?
Clinical and experimental evidence suggests that myocardial depression occurs during severe pancreatitis, but this evidence is derived from techniques that are not optimal for assessing myocardial contractility (e.g., rate of rise in ventricular pressure [dP/dt]). The slope of the left ventricular (LV) and systolic pressure dimension relationship (Ees), a better indicator of myocardial function, has not been measured in pancreatitis. Ten mongrel dogs underwent surgical instrumentation to monitor systemic arterial and LV pressure, cardiac output, LV dP/dt, and anterior LV wall thickness. End of systole was defined by the peak negative dP/dt. The end-systolic points used to calculate Ees were obtained by aortic and vena caval occlusion. After surgical recovery, pancreatitis was induced via cannulation of the pancreatic duct and injection of autologous bile (1 ml/kg) at 200 mm Hg perfusion pressure. All measurements were taken during a control period and daily after pancreatitis was induced. Pancreatitis was confirmed by a significant increase in serum amylase throughout the study and by autopsy finding of hemorrhagic necrosis. Ees was increased throughout the experimental protocol (1 to 7 days) (p less than 0.05). Myocardial performance as assessed by Ees was significantly increased and myocardial depression did not occur in untreated, conscious dogs with severe pancreatitis. Peak positive LV dP/dt was a poor index of contractility during pancreatitis since it decreased while myocardial contractility was increased. Cardiac depression in pancreatitis noted in other reports was likely due to decreased preload and not to intrinsic cardiac dysfunction.
Acute Disease↗
Skeletal muscle insulin unresponsiveness during chronic hyperdynamic sepsis in the dog.
Recent reports from our laboratory and others have documented changes in insulin unresponsiveness and electrolyte and hormonal changes characteristic of hypodynamic shock states in anesthetized animals. Since most acute shock protocols do not adequately mimic the clinical profile of sepsis, the present study was undertaken to document the hemodynamic and metabolic changes associated with chronic hyperdynamic peritonitis in dogs. Mongrel dogs of either sex weighing 20 +/- 2 kg were surgically instrumented with an electromagnetic aortic flow probe for monitoring cardiac output determinations, and aortic and central venous catheters for withdrawing blood for blood pressure and chemical analyses. Following a recovery period (7-10 days) control hemodynamic and metabolic measurements were made. Sepsis was induced (peritoneal abscess) by implanting a 4" X 4" gauze sponge, previously inoculated with human fecal bacteria, amid the intestines. Experimental (N = 18) and pair-fed control (N = 6) animals were monitored daily for 21 days or until death. During the septic protocol, cardiac index increased from a control value of 3.4 L/min/m2 to 5.5 L/min/m2 by the end of the experimental period. Mean arterial blood pressure, total peripheral resistance index, body weight, and plasma Ca++ fell below control values during the experimental period. Body temperature, plasma glucose, insulin, glucagon, and Mg++ were all elevated with sepsis. At the end of the chronic experimental period, skeletal muscle insulin responsiveness was assessed in the isolated, innervated, constantly perfused gracilis muscle preparation. Pair-fed control animals responded to various concentrations of local insulin infusion by increasing glucose uptake by the gracilis muscle. However, septic animals had a blunted response to local insulin infusion resulting in a decrease in the maximum dose response effect. These data demonstrate that: chronic, hyperdynamic peritonitis in the dog more closely mimics the human clinical profile of sepsis; and hyperdynamic sepsis is associated with a state of skeletal muscle insulin unresponsiveness which results from a post-receptor defect.
Abscess↗