Biomedical subjects

C J Hartley

Publications and source records attributed to C J Hartley.

At least 55 records · Page 3Linked to original sources

PubMed1990

Can pulsed Doppler technique measure changes in aortic blood flow in conscious rats?

To determine whether the pulsed Doppler (PD) system could be used to measure cardiac output we compared estimates of changes in aortic flow obtained from PD or electromagnetic (EM) probes on the ascending aorta in separate groups of conscious Long-Evans and Brattleboro rats under a variety of conditions. EM probes showed significant increases and decreases in aortic blood flow after administration of nitroprusside or methoxamine, respectively, but 20-MHz PD probes connected to a PD mainframe with a pulse repetition frequency (PRF) of 62.5 kHz showed no systematic changes in Doppler shift, due to "aliasing" of the Doppler signal. Aortic blood flow was significantly increased with intravenous volume expansion or isoprenaline administration, but these changes were not reliably detected by PD probes operating in a system with a PRF of 62.5 kHz. Calculation of expected peak Doppler shift signals from the phasic EM flow signal showed that these exceeded the Nyquist limit (PRF/2, i.e., 31.25 kHz) for the commercially available pulsed Doppler system. However, a modified pulsed Doppler module capable of resolving aliases and operating at a PRF of 125 kHz produced reliable results for changes in thoracic aortic Doppler shift, in good agreement with the EM probe data. In addition, placement of a cuff around the thoracic aorta did not alter cardiac baroreflex sensitivity.

Animals↗

PubMed1990

Central beta-adrenergic mechanisms may modulate ischemic ventricular fibrillation in pigs.

A central noradrenergic process may permit expression of the stress-related increase in cardiac vulnerability to ventricular fibrillation (VF). Thus, the effect of central beta-adrenergic receptor blockade with L-propranolol (0.01 and 0.05 mg/kg) on ischemia-induced VF vulnerability was evaluated in the psychologically stressed pig model and compared with Ringer's solution and D-propranolol (0.05 mg/kg). The ischemia of a maximum 15-minute left anterior descending coronary artery occlusion was used since we previously determined that pigs surviving 15 minutes usually do not fibrillate. Time to the onset of VF was analyzed by time-to-event analysis and ranged from 0.75 to 13.8 minutes in vulnerable pigs. Intracerebroventricular administration of L-propranolol (0.05 mg/kg) prolonged the time to VF compared with Ringer's solution and D-propranolol (p less than 0.05). The high dose of L-propranolol also reduced the incidence of VF (7/15 fibrillated) compared with Ringer's solution (12/12 fibrillated) and D-propranolol (6/7 fibrillated). The lower dose of L-propranolol was without effect on VF vulnerability (7/9) fibrillated). The plasma concentration resulting from central administration of 0.05 mg/kg L-propranolol was found to be 9.05 +/- 3.25 ng/ml, which is significantly below therapeutic antiarrhythmic blood levels. We conclude that the reduced vulnerability to ischemia-induced VF after intracerebroventricular administration of propranolol is due to alteration of a central beta-adrenergic receptor-mediated phenomenon as opposed to an effect on the heart directly or to nonspecific membrane stabilization.

Adaptation, Physiological↗

PubMed1990

Thromboxane B2 in cardiac lymph. Effect of superoxide dismutase and catalase during myocardial ischemia and reperfusion.

Neutrophils have been implicated in the genesis of myocardial ischemia-reperfusion injury, and their mechanism of action has been linked to the production of reactive oxygen species, fatty acid-derived prostanoids, and leukotrienes. In this study, we examined the potential relation between production of reactive oxygen species and cyclooxygenase-derived autacoids by studying the effects of superoxide dismutase (SOD) and catalase (CAT) on the rise in thromboxane formation observed with myocardial ischemia and reperfusion. Immunoreactive thromboxane B2 was measured in cardiac lymph from conscious dogs during reperfusion after a 60-minute occlusion in the presence of infusions of SOD alone, CAT alone, and a combination of SOD and CAT. Reperfusion after 60 minutes of ischemia causes an immediate elevation in thromboxane B2. SOD and CAT infusion prevented this rise in thromboxane B2 as did infusion of SOD alone. The ability of SOD-CAT to suppress thromboxane B2 production dissipated within 3 hours after the cessation of infusion, at which time thromboxane B2 excretion increased. The modulation of fatty acid oxygenases by reactive oxygen species may be a very important pathogenic factor in considering the origin of the protective effect of antioxidants in the setting of myocardial ischemia-reperfusion injury.

Animals↗

PubMed1990

Implantable sensor for intraoperative and postoperative monitoring of blood flow: a preliminary report.

We have developed an implantable 20 MHz Doppler flow sensor, to monitor blood flow in patients after operation. During surgery the sensor is wrapped around a blood vessel and secured in place with a releasable tie. No tissue puncturing techniques are required. The lead wires, together with a release cable, are exteriorized through the chest wall. Several days after operation, the tie is externally released, and the sensor is pulled out. Twenty-seven sensors were implanted in 24 dogs for up to 16 days. All were extracted successfully with minimal visible behavioral reaction in the awake dogs and caused no thrombosis or vascular damage. The Doppler velocity signals had excellent linear correlations (r = 0.99) with data from electromagnetic flow sensors and timed blood collections. In addition, the sensors were applied to coronary artery bypass grafts in 31 patients for up to 2 days after operation. High-quality signals were obtained, and intraoperatively recorded signals agreed well with simultaneous electromagnetic flow tracings. All sensors were extracted with minimal discomfort to the awake patients and with no complications. Thus, the implantable flow sensor is a safe, reliable, accurate, and simple method for intraoperative and postoperative monitoring of blood flow in vessels 2.5 to 5 mm in diameter.

Animals↗

PubMed1989

Review of intracoronary Doppler catheters.

During the last 20 years several types of Doppler catheters have been developed and applied to the measurement of coronary blood flow velocity in man. Validation studies in the laboratory and in animals have shown that these catheters can accurately measure velocity from a small sample volume beside or ahead of the catheter tip. The Doppler transducers have been miniaturized enough (less than 1 mm dia) to be mounted on subselective coronary catheters or balloon angioplasty catheters without compromising any of the normal catheter functions. Good quality, high fidelity velocity signals have been recorded from many sites within the coronary circulation of patients during coronary arteriography and balloon angioplasty. Coronary flow reserve measured with Doppler catheters is a physiologic index of the severity of a stenosis which, when carefully measured, can be used for assessing lesions, planning treatment, and evaluating the success of interventions.

Blood Flow Velocity↗

PubMed1989

Prolonged abnormalities of left ventricular diastolic wall thinning in the "stunned" myocardium in conscious dogs: time course and relation to systolic function.

Myocardial reperfusion after reversible ischemia is known to be associated with prolonged abnormalities of systolic contractile function (myocardial "stunning"). However, no information is available regarding the recovery of diastolic function in the stunned myocardium in the conscious state. Accordingly, 10 conscious dogs instrumented with pulsed Doppler thickening probes underwent a 15 min occlusion of the left anterior descending coronary artery followed by 7 days of reperfusion. Regional systolic function was assessed as net systolic thickening fraction. Left ventricular regional diastolic properties were estimated from two variables: the mean rate to half end-diastolic thinning and the late diastolic thinning fraction. Both indexes of diastolic function remained severely impaired after restoration of flow. In general, the recovery of the mean rate to half end-diastolic thinning and of the late diastolic thinning fraction paralleled the recovery of systolic thickening, but the impairment of the mean rate to half end-diastolic thinning was more marked than that of the late diastolic thinning fraction. At 4 h of reperfusion, the values for the mean rate to half end-diastolic thinning and the late diastolic thinning fraction (expressed as percent of baseline) were 57 +/- 5% (p less than 0.001 versus baseline) and 79 +/- 7% (p less than 0.05), respectively, whereas systolic thickening fraction averaged 52 +/- 10% (p less than 0.001). At 24 h, the mean rate to half end-diastolic thinning and the late diastolic thinning fraction were no longer significantly different from baseline, whereas systolic thickening fraction remained decreased at 82 +/- 4% (p less than 0.001) and returned to control values by 48 h. This study demonstrates the presence of profound, prolonged abnormalities of regional diastolic wall thinning after a brief episode of ischemia in the conscious state and expands the concept of myocardial stunning from the traditional notion of impaired systolic performance to that of a global derangement in mechanical function that involves both systolic and diastolic properties.

Animals↗

PubMed1989

Cardiovascular effects of and interaction between calcium blocking drugs and anesthetics in chronically instrumented dogs: VII. Verapamil and thiopental.

To assess the role of basal anesthesia in the negative inotropic properties of verapamil, the effect of thiopental (30 mg/kg followed by 3.5 mg.kg-1.min-1) on verapamil pharmacokinetics (200 micrograms/kg iv; n = 6) and its pharmacodynamics (3 and 6 micrograms.kg-1.min-1; n = 11) in chronically instrumented dogs was studied. In the presence of thiopental, verapamil pharmacokinetics remained essentially unchanged. In contrast, anesthesia altered verapamil hemodynamic properties. In the conscious animal verapamil infusions increased heart rate (14 +/- 3 and 27 +/- 4 beats/min, respectively), cardiac output (0.22 +/- 0.07 and 0.24 +/- 0.08, l/min, respectively) and PR interval (14 +/- 2 and 25 +/- 6 ms, respectively) and slightly decreased dP/dt (-315 +/- 114 and -419 +/- 106 mmHg/s, respectively). Systemic vascular resistance (SVR) decreased at the low dose (-2.7 +/- 0.7 mmHg.1.min-1), and stroke volume decreased at the high dose (-4.4 +/- 0.6 ml). Yet the presence of thiopental resulted in an accentuation of verapamil-induced tachycardia (27 +/- 7 and 31 +/- 6 beats/min, respectively), and a decrease in stroke volume (-5.3 +/- 2.0 and -6.3 +/- 2.1 ml, respectively). At 3 micrograms.kg-1.min-1 verapamil did not increase PR interval, cardiac output, or vasodilation. Finally, at 6 micrograms.kg-1.min-1 verapamil did not decrease dP/dt and increased renal blood flow (21.8 +/- 6.4 ml/min). These data provide evidence that the negative inotropic properties of verapamil are more pronounced in the presence of thiopental. However, the role of basal anesthesia appears to be limited.

Animals↗

PubMed1989

Nonuniform transmural recovery of contractile function in stunned myocardium.

With the use of an epicardial Doppler probe, systolic wall thickening was selectively measured in the inner, mid, and outer layers of the left ventricular (LV) wall in 16 conscious dogs undergoing a 15-min left anterior descending artery (LAD) occlusion followed by 7 days of reperfusion (REP). Under control conditions, percent thickening fraction (ThF) was significantly greater (P less than 0.01) in the inner layer [36.0 +/- 2.3% (mean +/- SE)] than in the mid (28.6 +/- 2.1%) or outer (21.3 +/- 2.2%) layers. During LAD occlusion, 11 dogs exhibited transmural dyskinesis (group 1), whereas 5 had transmural hypokinesis (group 2). In group 1, all layers exhibited comparable degrees of paradoxical systolic thinning during LAD occlusion. After REP, however, recovery was delayed in the inner compared with the mid and outer layers. At 2 h, ThF averaged 34.2 +/- 11.9% of base line in the endocardium vs. 61.7 +/- 16.2% in the midmyocardium and 51.0 +/- 12.3% in the epicardium (F = 4.29, P less than 0.002); similar differences were noted at 3 and 4 h. In the mid and outer layers, ThF returned to base-line values by 24 h, whereas in the inner layer it was still significantly depressed (P less than 0.05) at 24 h (77.3 +/- 5.1% of base line) and recovered by 48 h. The inner-to-outer ThF ratio was decreased (P less than 0.01) for 24 h after REP, indicating maldistribution of thickening in the "stunned" myocardium. In group 2, all layers exhibited hypokinesis during LAD occlusion. Again, recovery of function after REP was delayed in the endocardium compared with the other layers. This study demonstrates that after both severe ischemia resulting in dyskinesis and mild ischemia resulting in hypokinesis, REP is associated with slower recovery of function in the inner than in the outer layers. Thus myocardial "stunning" is a nonuniform phenomenon with maximal severity in the subendocardium.

Animals↗

PubMed1988

Quantitative assessment of left ventricular wall motion by two-dimensional echocardiography: validation during reversible ischemia in the conscious dog.

This study was designed to test the accuracy of echocardiographic radial shortening measurements during variable degrees of regional dysfunction produced by 14 transient (less than or equal to 10 min) coronary occlusions (8 left anterior descending coronary artery, 6 left circumflex coronary artery) followed by up to 24 h of reperfusion in chronically instrumented conscious dogs. Independent measurement of regional myocardial thickening was obtained using epicardial pulsed Doppler probes and served as a standard for comparison. Radial shortening fraction was derived from two-dimensional short-axis views along 12 equidistant radii. Six reference systems from the epicardial and endocardial centers of geometry (centroids) in a fixed or a floating position were explored. In the ischemic zone, percent thickening fraction averaged 22 +/- 5% at baseline, decreased to -4 +/- 4% during occlusion and gradually returned to baseline values after reperfusion. Percent change in radial shortening correlated significantly with percent change in thickening fraction in the ischemic zone. The worst correlation was seen with the floating endocardial centroid (r = 0.68), and the best was observed with the epicardial floating reference (r = 0.91). Moreover, the epicardial floating reference provided narrower 95% confidence limits of radial shortening and less heterogeneity among radii than did fixed reference systems. Thus, compared with an independent standard, echocardiographic measurement of radial shortening from the short axis provided recognition of discrete grades of regional dysfunction induced by transient reversible ischemia. This technique may be amenable for serial assessment of regional function after interventions on the ischemic myocardium.

Animals↗

PubMed1988

Regional blood flows and cardiac function changes induced by angiotensin II in conscious dogs.

Hemodynamic properties of angiotensin (ANG) II 1, 5, 10 and 100 ng/kg i.v. and 10, 100 and 1000 ng/kg i.v.t. were assessed in conscious dogs. ANG II i.v. produced a dose-dependent pressor response (59 +/- 5-124 +/- 16 mmHg) and renal vasoconstriction (1.3 +/- 0.4-96 +/- 32 mmHg/ml/min). Ganglionic blockade (chlorisondamine 2 mg/kg i.v.) diminished mean arterial responses without altering peptide effects on renal circulation. At the highest dose, ANG II i.v. induced cardiac stimulation: increased heart rate (75 +/- 4-115 +/- 6 beats/min), cardiac output (2.0 +/- 0.1-2.4 +/- 0.2 l/min), dP/dt (2308 +/- 181-2773 +/- 173 mmHg/sec) and coronary blood flow (49 +/- 10-96 +/- 23 ml/min). Although with chlorisondamine cardiac response was more pronounced, subsequent beta blockade abolished it. Concomitantly, an isolated increase in plasma epinephrine was recorded (63 +/- 8-1505 +/- 354 pg/ml). A pressor response (59 +/- 8-89 +/- 13 mmHg) and renal vasoconstriction (1.1 +/- 0.1-2.2 +/- 0.5 mmHg/ml/min) were also produced by ANG II i.v.t. at the highest dose. These centrally mediated changes were prevented by chlorisondamine. Our study demonstrates 1) i.v. ANG II-mediated pressor responses are dependent on direct and indirect components, the relative contribution of each being dependent on the regional circulation; ANG II i.v. also produced a biphasic cardiac response--an initial centrally mediated depression and a secondary stimulation dependent on epinephrine via cardiac beta receptors and 2) i.v.t. ANG II-mediated pressor effects are essentially indirect. Finally, no evidence was found to support the role of vasopressin in ANG II effects.

Angiotensin II↗

PubMed1987

In vivo assessment of vascular dilatation during percutaneous transluminal coronary angioplasty.

Previous studies of the mechanism of percutaneous transluminal coronary angioplasty used either postmortem specimens or animal models. To characterize the process of vascular dilatation in vivo, a system was devised for recording the instantaneous pressure-volume changes in the angioplasty balloon during inflation within the stenosed artery. The pressure-volume patterns obtained were compared with those observed in vitro with the balloon inflated in materials whose properties simulate stretching (Silastic tubing), compaction (styrofoam) and cracking (dry macaroni). Of 48 narrowings in 46 patients, a pressure-volume pattern of stretching was observed in 56%, compaction in 27% and cracking in only 17%. Of lesions manifesting a stretching pattern, 85% were longer than 5 mm cr had visible calcium deposits, whereas those that compacted were shorter and lacked calcium deposits. Both of these pressure-volume patterns were associated with a successful clinical outcome. Of 8 lesions exhibiting a cracking pattern, 6 showed dissection angiographically; 3 of these resulted in vessel occlusion.

Angioplasty, Balloon↗

PubMed1987

End-systolic radius to thickness ratio: an echocardiographic index of regional performance during reversible myocardial ischemia in the conscious dog.

Regional myocardial dysfunction induced by ischemia is associated with less thickening and a larger ventricular radius at end-systole. Thus, end-systolic radius to thickness ratio measured by echocardiography may provide an accurate index of regional left ventricular function that is totally independent of cardiac motion. To test this hypothesis, a total of 14 transient (less than or equal to 10 minutes) coronary artery occlusions (8 left anterior descending, 6 left circumflex) followed by up to 24 hours of reperfusion were performed in six chronically instrumented conscious dogs providing multiple grades of regional ventricular dysfunction. Regional myocardial thickening fraction was determined with epicardial pulsed Doppler probes and served as an independent standard for comparison with simultaneous echocardiographic measurements. End-systolic radius to thickness ratio and radial shortening fraction were derived from the two-dimensional echocardiographic short-axis view along 12 equidistant radii. In the ischemic zone, percent thickening fraction averaged 22 +/- 5% during baseline, decreased to -4 +/- 4% during occlusion with gradual return to baseline after reperfusion. End-systolic radius to thickness ratio averaged 1.39 +/- 0.25 before coronary occlusion and increased to 2.97 +/- 0.48 during occlusion with a gradual return to baseline values. A significant correlation was found between Doppler-determined thickening fraction measurements and echocardiographic end-systolic radius to thickness ratio as well as radial shortening fraction for absolute values (r = -0.83 and 0.75, respectively; n = 65) and percent change from baseline (r = -0.86 and 0.78, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Lipoxygenase inhibitor nafazatrom fails to attenuate postischaemic ventricular dysfunction.

The role of lipoxygenase activation in the genesis of postischaemic myocardial dysfunction was investigated in open chest dogs undergoing a 15 min occlusion of the left anterior descending artery followed by 4 h of reperfusion. Treated animals (n = 9) received nafazatrom, a potent lipoxygenase inhibitor, 10 mg.kg-1 orally 4 h before occlusion followed by intravenous boluses of 1.5 mg.kg-1 and 0.5 mg.kg-1 5 min before occlusion and 1 min before reperfusion respectively. Control animals (n = 10) received saline. No discernible haemodynamic effects were produced by the drug. Collateral flow to the ischaemic zone (radioactive microspheres) was 0.14(0.02) ml.min-1.g-1 in the control group and 0.16(0.05) ml.min-1.g-1 in the treated group. The size of the occluded bed as determined by postmortem perfusion was 25.5(0.8)% of the left ventricle in the control and 24.3(1.3)% in the treated group. Histological examination showed a decrease in neutrophil infiltration of the non-ischaemic myocardium and, to a lesser extent, of the reperfused myocardium in nafazatrom treated animals, suggesting lipoxygenase inhibition. Systolic wall thickening (an index of regional function) was assessed using an epicardial pulsed Doppler probe. The two groups exhibited comparable systolic thickening under baseline conditions. Though treated animals showed less dyskinesis during coronary occlusion (p less than 0.05), recovery of function was not enhanced over controls and in both groups the reperfused myocardium was still dyskinetic at 4 h. Thus nafazatrom failed to improve postischaemic ventricular dysfunction, suggesting that leukotrienes do not contribute importantly to this phenomenon.

Animals↗

PubMed1987

Cardiovascular effects of and interaction between calcium blocking drugs and anesthetics in chronically instrumented dogs. IV. Chronically administered oral verapamil and halothane, enflurane, and isoflurane.

Dogs were chronically instrumented to measure aortic and left atrial blood pressures, left ventricular maximal rate of tension development (dP/dt), cardiac output, and carotid, coronary and renal blood flows. Measurements were taken with the animals awake and during steady-state low and high concentrations of halothane (1.2%, 2.4%), enflurane (2.4%, 4.0%), and isoflurane (1.6%, 3.0%) with and without at least 2 weeks of oral verapamil, 120 mg, three times per day. Plasma verapamil levels varied widely, with means of 500-700 ng X ml-1 in awake animals and lower (300-400 ng X ml-1) at the time of hemodynamic measurements during anesthesia. Chronic oral verapamil in awake dogs produced predominantly tachycardia. The hemodynamic effects of low-dose halothane and isoflurane before and after oral verapamil were unchanged except for decreased renal blood flow after oral verapamil and no coronary vasodilation nor tachycardia. However, left atrial pressure was increased and cardiac output and coronary blood flow were decreased by low concentrations of enflurane with oral verapamil compared to without. The combination of oral verapamil with low (clinical) doses of enflurane was more depressant to the cardiovascular system of healthy dogs than was the combination of verapamil and halothane or isoflurane.

Administration, Oral↗

PubMed1987

First-pass hepatic extraction and metabolic effects of insulin and insulin analogues.

First-pass hepatic extraction of insulin and hepatic and peripheral contributions to hypoglycemia were compared in conscious dogs during portal infusion of insulin A1, B29 diacetyl insulin, or A1-B29 dodecoyl insulin at 7 and 14 pmol X kg-1 X min-1. The liver removed 43 +/- 2% of insulin, 12 +/- 1% of dodecoyl, and 8 +/- 1% of diacetyl insulin, in a single transhepatic circulation. The hypoglycemia induced by insulin and diacetyl insulin and the ensuing glucagon response were greater than that produced by the dodecoyl analogue. Diacetyl insulin primarily increased glucose utilization, dodecoyl insulin solely inhibited hepatic production, and insulin affected both. The lack of hepatic effect of diacetyl insulin during hypoglycemia can be ascribed to greater counterregulation, because under euglycemic clamp conditions, this analogue caused suppression of glucose production. The different patterns of hypoglycemia exhibited can be explained by the combined effects of altered distribution between the liver and peripheral tissues caused by differences in hepatic extraction, the effect of this phenomenon on the counterregulatory response, and the intrinsic biological potency of the analogues.

Animals↗

PubMed1987

The iron chelator desferrioxamine attenuates postischemic ventricular dysfunction.

Recent evidence suggests that postischemic myocardial dysfunction ("stunning") may be mediated by oxygen free radicals, but the mechanism by which they produce myocellular damage remains unknown. Since iron catalyzes formation of hydroxyl radicals (HO.) as well as HO.-initiated lipid peroxidation, we explored the potential role of this metal in the pathogenesis of myocardial stunning. Open-chest dogs undergoing a 15-min occlusion of the left anterior descending coronary artery (LAD) followed by 4 h of reperfusion (REP) received the iron chelator desferrioxamine intravenously (10 mg/kg over 45 min beginning 30 min before occlusion, then 1.7 mg.kg-1.h-1 throughout REP, n = 19) or normal saline (n = 17). Regional myocardial function was assessed by measuring systolic wall thickening with an epicardial Doppler probe. The two groups exhibited comparable systolic thickening under base-line conditions and similar degrees of dyskinesis during ischemia. After REP, however, recovery of contractile function (expressed as percent systolic thickening) as considerably greater in desferrioxamine-treated compared with control dogs: 5 +/- 3 (mean +/- SE) vs. -3 +/- 2% (P less than 0.05) at 1 h, 6 +/- 3 vs. -2 +/- 3% (P less than 0.05) at 2 h, 5 +/- 3 vs. -6 +/- 2% (P less than 0.005) at 3 h, and 6 +/- 3 vs. -6 +/- 2% (P less than 0.002) at 4 h. These differences could not be ascribed to hemodynamic factors. The results suggest that iron-catalyzed reactions (possibly HO. generation) play a significant role in myocardial stunning after a brief episode of reversible regional ischemia.

Animals↗

PubMed1987

Attenuation of dysfunction in the postischemic 'stunned' myocardium by dimethylthiourea.

The mechanism for the prolonged contractile dysfunction observed in myocardium reperfused after reversible regional ischemia ("stunned" myocardium) is unclear. Recent studies suggest that myocardial stunning may be mediated by oxygen-derived free radicals, but the precise molecular species involved remain unknown. Thus we explored the role of the highly cytotoxic hydroxyl radical in regional postischemic dysfunction by using dimethylthiourea (DMTU), an effective and highly permeable hydroxyl radical scavenger. Open-chest dogs undergoing a 15 min occlusion of the left anterior descending coronary artery followed by 4 hr of reperfusion received either DMTU (0.5 g/kg iv over 45 min starting 30 min before occlusion, n = 14) or saline (n = 15). Control and treated dogs were comparable with respect to variables that may affect postischemic dysfunction, including heart rate, aortic pressure, left atrial pressure, arterial blood gases and hemoglobin concentration, size of the occluded bed (determined by postmortem perfusion), and collateral blood flow (determined by radioactive microspheres). Regional myocardial function was assessed by measuring wall thickening with an epicardial Doppler probe. The two groups exhibited comparable systolic thickening under baseline conditions and similar degrees of dyskinesis during ischemia. After reperfusion, however, wall thickening (expressed as percent of baseline) was considerably greater in treated as compared with control dogs: 53 +/- 9% (mean +/- SEM) vs 9 +/- 14% (p less than .03) at 1 hr, 55 +/- 9% vs 23 +/- 13% (p less than .05) at 2 hr, 60 +/- 9% vs 28 +/- 14% (p less than .05) at 3 hr, and 67 +/- 5% vs 36 +/- 13% (p less than .05) at 4 hr. Thus DMTU produced a significant and sustained improvement in recovery of contractile function. In concentrations greater than the plasma levels attained in vivo, DMTU did not scavenge either hydrogen peroxide or superoxide anion in vitro. These results suggest that the myocardial dysfunction occurring after a brief episode of regional ischemia is mediated in part by the hydroxyl radical.

Animals↗

PubMed1987

Role of isoflurane on hemodynamic properties and disposition of nicardipine.

Nicardipine properties (30 micrograms/kg i.v.) were studied in a group of eight dogs awake and anesthetized with isoflurane 1.6% end-tidal. Awake, nicardipine produced a decrease in mean arterial pressure (-12 +/- 2 mm Hg) associated with an increase in cardiac output (1.63 +/- 0.2 liters/min), heart rate (75 +/- 9 beats/min), dP/dt (741 +/- 202 mm Hg/sec) and carotid (41 +/- 11 ml/min) and coronary blood flows (39 +/- 6 ml/min). During isoflurane, responses to nicardipine injections were less pronounced except for mean arterial pressure (-19 +/- 2 mm Hg) and reversed for dP/dt (-290 +/- 63 mm Hg/sec). In a second group of six conscious dogs, nicardipine (30 micrograms/kg i.v.) injected after ganglionic blockade (chlorisondamine, 2 mg/kg i.v.) elicited changes similar to those recorded during isoflurane anesthesia, data that demonstrated the importance of isoflurane-induced baroreflex blockade as a mechanism of the pharmacodynamic interactions between nicardipine and isoflurane. Isoflurane reduced nicardipine initial volume of distribution (11.6 +/- 1.2 vs. 8.9 +/- 0.8 liters), total clearance (28.5 +/- 2.9 vs. 19.2 +/- 2.1 liters/hr) and volume of distribution at steady state (50.0 +/- 11.3 vs. 29.2 +/- 3.7 liters, P less than .05). Nicardipine-induced hemodynamic changes were linearly correlated with the drug concentrations in plasma. In the presence of isoflurane, the slopes of these relationships were reduced for all hemodynamic variables except for mean arterial pressure, for which the slope was more pronounced, and dP/dt, for which the slope was reversed. In conclusion, isoflurane alters the drug plasma concentration-effect relationship of nicardipine as a result of both pharmacokinetic and pharmacodynamic interactions.

Animals↗