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J R Kersten

Publications and source records attributed to J R Kersten.

54 records · Page 3Linked to original sources
PubMed1997

The effects of isoflurane and halothane on left ventricular afterload in dogs with dilated cardiomyopathy.

UNLABELLED: The effects of volatile anesthetics, including isoflurane (ISO) and halothane (HAL), on determinants of left ventricular (LV) afterload have not been comprehensively described in experimental models of, or patients with, heart failure. We tested the hypothesis that ISO and HAL produce beneficial alterations in LV afterload when evaluated with aortic input impedance and interpreted using a three-element Windkessel model in dogs before and after development of pacing-induced cardiomyopathy. Hemodynamics and aortic pressure and blood flow waveforms were recorded in the conscious state and during 1.1- and 1.5-minimum alveolar anesthetic concentration (MAC) ISO and HAL anesthesia on separate days in chronically instrumented dogs (n = 6). Dogs were then paced at 220-240 bpm for 20 +/- 3 days (mean = SEM) to develop cardiomyopathy, and the experiments were repeated after pacing had been temporarily discontinued. ISO decreased mean arterial pressure (MAP), mean aortic blood flow (MAQ), and total arterial resistance (R) and increased total arterial compliance (C) and characteristic aortic impedance (Zc) in dogs before pacing. HAL decreased MAP and MAQ and increased C but did not alter R and Zc. Chronic rapid LV pacing increased HR and LV end-diastolic pressure and decreased MAP, LV systolic pressure, and the peak rate of increase of LV pressure. MAQ, C, R, and Zc were unchanged. ISO and HAL decreased arterial pressure but did not affect C and Zc in the presence of LV dysfunction. HAL, but not ISO, increased R at 1.1 MAC, which indicates that this drug increases resistance to LV ejection. In contrast to findings in normal dogs, these results indicate that neither ISO nor HAL reduce arterial hydraulic resistance to LV ejection or favorably improve the rectifying properties of the aorta in dogs with pacing-induced cardiomyopathy. IMPLICATIONS: Isoflurane and halothane produce favorable alterations in the determinants of left ventricular afterload before, but not after, the production of experimental left ventricular dysfunction by sustained, rapid cardiac pacing in chronically instrumented dogs.

Anesthetics, Inhalation↗
PubMed1997

Role of adenosine in isoflurane-induced cardioprotection.

BACKGROUND: This investigation tested the hypothesis that adenosine (A1) receptor blockade modulates the cardioprotective effects of isoflurane. METHODS: Hemodynamics and percentage segment shortening (%SS) in the left anterior descending coronary artery (LAD) perfusion territory were evaluated in barbiturate-anesthetized dogs (n = 31) at selected intervals after pretreatment with the selective A1 receptor antagonist (8-cyclopentyl-1,3,dipropyl-xanthine; DPCPX 0.8 mg/kg, intravenously) or drug vehicle in the presence or absence of 1 minimum alveolar concentration (MAC) isoflurane. Dogs were subjected to five 5-min occlusions and reperfusions of the LAD, followed by 180 min of final reperfusion. Isoflurane was administered for 30 min before and during LAD occlusions and reperfusions and was discontinued at the onset of final reperfusion. Two other groups of dogs (n = 17) were used to measure interstitial concentrations of purines in the LAD region using a microdialysis technique in the presence and absence of isoflurane. RESULTS: Dogs receiving drug vehicle or DPCPX exhibited no recovery of %SS after 180 min of reperfusion (-5 +/- 7 and 5 +/- 11% of baseline, respectively, +/- SEM). In contrast, dogs receiving isoflurane alone demonstrated complete recovery of %SS at 60 min after reperfusion. DPCPX pretreatment partially attenuated isoflurane-induced enhancement of recovery of %SS (34 +/- 11% of baseline 180 min after reperfusion; P < 0.05). Interstitial purine concentrations were increased during multiple occlusions and reperfusions of the LAD in dogs not receiving isoflurane, but they were unchanged by coronary artery occlusion and reperfusion in dogs receiving isoflurane. CONCLUSIONS: The results indicate that isoflurane-induced cardioprotection in stunned myocardium is partially mediated by adenosine type 1 receptor activation and is accompanied by decreases in endogenous adenosine release.

Anesthetics, Inhalation↗
PubMed1997

Positive inotropic and lusitropic effects of triiodothyronine in conscious dogs with pacing-induced cardiomyopathy.

BACKGROUND: The effects of triiodothyronine (T3) on systemic hemodynamics, myocardial contractility (preload recruitable stroke work slope; Mw), and left ventricular (LV) isovolumic relaxation (time constant; tau) were examined before and after the development of pacing-induced cardiomyopathy in conscious dogs. METHODS: Dogs (n = 8) were chronically instrumented for measurement of aortic and LV pressure, dP/dtmax, subendocardial segment length, and cardiac output. Dogs received escalating doses (0.2, 2.0, and 20.0 mg/kg, intravenous) of T3 over 5 min at 1-h intervals, and peak hemodynamic effects were recorded 10 min after each dose and 24 h after the final dose. Dogs were then continuously paced at 220-240 beats/min for 21 +/- 2 days. Pacing was temporarily discontinued after the development of severe LV dysfunction, and administration of T3 was repeated. RESULTS: T3 produced immediate and sustained (24 h) increases (P < 0.05) in Mw and dP/dtmax in dogs before the initiation of pacing, consistent with a positive inotropic effect. No changes in tau occurred. Rapid ventricular pacing over 3 weeks increased baseline heart rate (sinus rhythm) and LV end-diastolic pressure, decreased mean arterial and LV systolic pressures, and caused LV systolic (decreases in Mw and dP/dtmax) and diastolic (increases in tau) dysfunction. T3 caused immediate and sustained increases in Mw (63 +/- 7 during control to 82 +/- 7 mmHg after the 2 mg/kg dose) and decreases in tau (65 +/- 8 during control to 57 +/- 6 ms after the 20 mg/kg dose), indicating that this hormone enhanced myocardial contractility and shortened LV relaxation, respectively, in the presence of chronic LV dysfunction. In contrast to the findings in dogs with normal LV function, T3 did not affect heart rate and calculated indices of myocardial oxygen consumption and reduced LV end-diastolic pressure (27 +/- 3 during control to 20 +/- 2 mmHg after the 2 mg/kg dose) in cardiomyopathic dogs. CONCLUSIONS: The findings indicate that T3 produces favorable alterations in hemodynamics and modest positive inotropic and lusitropic effects in conscious dogs with LV dysfunction produced by rapid LV pacing.

Animals↗
PubMed1997

Isoflurane mimics ischemic preconditioning via activation of K(ATP) channels: reduction of myocardial infarct size with an acute memory phase.

BACKGROUND: The authors tested the hypothesis that isoflurane directly preconditions myocardium against infarction via activation of K(ATP) channels and that the protection afforded by isoflurane is associated with an acute memory phase similar to that of ischemic preconditioning. METHODS: Barbiturate-anesthetized dogs (n = 71) were instrumented for measurement of systemic hemodynamics. Myocardial infarct size was assessed by triphenyltetrazolium chloride staining. All dogs were subjected to a single prolonged (60 min) left anterior descending coronary artery (LAD) occlusion followed by 3 h of reperfusion. Ischemic preconditioning was produced by four 5-min LAD occlusions interspersed with 5-min periods of reperfusion before the prolonged LAD occlusion and reperfusion. The actions of isoflurane to decrease infarct size were examined in dogs receiving 1 minimum alveolar concentration (MAC) isoflurane that was discontinued 5 min before prolonged LAD occlusion. The interaction between isoflurane and ischemic preconditioning on infarct size was evaluated in dogs receiving isoflurane before and during preconditioning LAD occlusions and reperfusions. To test whether the cardioprotection produced by isoflurane can mimic the acute memory of ischemic preconditioning, isoflurane was discontinued 30 min before prolonged LAD occlusion and reperfusion. The mechanism of isoflurane-induced cardioprotection was evaluated in two final groups of dogs pretreated with glyburide in the presence or absence of isoflurane. RESULTS: Myocardial infarct size was 25.3 +/- 2.9% of the area at risk during control conditions. Isoflurane and ischemic preconditioning produced significant (P < 0.05) and equivalent reductions in infarct size (ischemic preconditioning alone, 9.6 +/- 2.0; isoflurane alone, 11.8 +/- 2.7; isoflurane and ischemic preconditioning, 5.1 +/- 1.9%). Isoflurane-induced reduction of infarct size also persisted 30 min after discontinuation of the anesthetic (13.9 +/- 1.5%), independent of hemodynamic effects during LAD occlusion. Glyburide alone had no effect on infarct size (28.3 +/- 3.9%), but it abolished the protective effects of isoflurane (27.1 +/- 4.6%). CONCLUSIONS: Isoflurane directly preconditions myocardium against infarction via activation of K(ATP) channels in the absence of hemodynamic effects and exhibits acute memory of preconditioning in vivo.

Anesthetics, Inhalation↗
PubMed1997

Isoflurane and halothane do not alter the enhanced afterload sensitivity of left ventricular relaxation in dogs with pacing-induced cardiomyopathy.

BACKGROUND: The afterload dependence of left ventricular (LV) relaxation is accentuated in the failing heart. The authors tested the hypothesis that isoflurane and halothane alter the afterload sensitivity of LV relaxation in dogs with pacing-induced cardiomyopathy. METHODS: Dogs (n = 6) were chronically instrumented for measurement of LV and aortic pressures and subendocardial segment length. Hemodynamics were recorded, and LV relaxation was evaluated with a time constant of isovolumic relaxation (tau) under control conditions and during decreases and increases in LV load produced by abrupt inferior vena caval (IVC) occlusion and phenylephrine (intravenous infusion), respectively, in the conscious state and during isoflurane and halothane anesthesia (1.5 MAC) on separate days before and after the development of pacing-induced cardiomyopathy. The slope (R) of the tau versus LV end-systolic pressure (P[es]) relation was also used to determine the afterload sensitivity of LV relaxation. RESULTS: IVC occlusion and phenylephrine produced similar or less profound changes in P(es), regional end-systolic force (an index of LV afterload), and end-systolic segment length in cardiomyopathic compared with healthy dogs. However, IVC occlusion and phenylephrine caused more pronounced alterations in tau in conscious and isoflurane- and halothane-anesthetized dogs after the development of cardiomyopathy. R was also greater in cardiomyopathic compared with healthy dogs (e.g., 0.32 +/- 0.03 before pacing to 1.00 +/- 0.13 ms/mmHg in conscious dogs). No differences in the load dependence of LV relaxation were observed between the conscious and anesthetized states before and after production of LV dysfunction. CONCLUSIONS: The results indicate that isoflurane and halothane do not alter the afterload dependence of LV relaxation in the normal and cardiomyopathic heart. The lack of effect of the volatile anesthetics is probably related to anesthetic-induced reductions in the resistance to LV ejection concomitant with simultaneous negative inotropic effects.

Anesthetics, Inhalation↗
PubMed1996

Glyburide, a KATP channel antagonist, attenuates the cardioprotective effects of isoflurane in stunned myocardium.

This investigation examined the role of myocardial adenosine triphosphate-regulated potassium (KATP) channels in isoflurane-induced enhancement of myocardial function after reversible tissue injury produced by a 15-min left anterior descending coronary artery occlusion (LAD) and reperfusion. Dogs (n = 14) were chronically instrumented for measurement of left ventricular (LV) and aortic blood pressure, cardiac output, coronary blood flow velocity, and subendocardial segment length. Regional myocardial contractility was evaluated with preload recruitable work area (PRWA). Isovolumic relaxation was assessed with a time constant (tau). Hemodynamic variables and LV function were measured in the conscious state, during 2% isoflurane anesthesia for 45 min before and during a 15-min LAD occlusion, and at several intervals after reperfusion in dogs pretreated with glyburide (0.3 mg/kg, intravenously) or drug vehicle. LAD occlusion caused regional dyskinesia and increases in tau. Vehicle-pretreated dogs demonstrated full recovery of segment shortening by 5 h postreperfusion and recovery of PRWA and tau by 30 min postreperfusion. In contrast, dogs pretreated with glyburide demonstrated sustained systolic and diastolic dysfunction. Segment shortening recovered to only 70% +/- 5%, PRWA remained depressed at 48% +/- 10% and tau was prolonged to 116% +/- 5% of control values at 5 h postreperfusion. The results indicate that isoflurane enhances recovery of myocardial contractile function by 5 h postreperfusion, in comparison to previous findings in conscious dogs. These effects are partially blocked by glyburide pretreatment, indicating that KATP channel activation by isoflurance may mediate these cardioprotective effects.

Anesthetics, Inhalation↗
PubMed1996

Isoflurane, but not halothane, improves indices of diastolic performance in dogs with rapid ventricular, pacing-induced cardiomyopathy.

BACKGROUND: The left ventricular (LV) mechanical effects of isoflurane and halothane were examined in dogs with rapid LV pacing-induced cardiomyopathy. These experiments tested the hypothesis that isoflurane and halothane differentially enhance indices of diastolic performance in dogs with moderate LV dysfunction. METHODS: Eight dogs were chronically instrumented for measurement of LV and aortic pressures, subendocardial segment length, and cardiac output. Contractility was quantified by preload recruitable stroke work (Mw). Diastolic function was evaluated with a time constant of isovolumic relaxation (tau), segment lengthening velocities and time-velocity integrals during early filling (dL/dtE and TVI-E) and atrial systole (dL/dtA and TVI-A), and a regional chamber stiffness constant (Kp). Hemodynamics and LV function were recorded in the conscious state before pacing. The left ventricles of the dogs were then continuously paced at ventricular rates between 220 and 240 beats.min-1 for 10 +/- 1 days and monitored on a daily basis. After the development of moderate LV dysfunction, pacing was temporarily discontinued, and dogs were studied in sinus rhythm in the conscious state and after 20 min equilibration at 1.1, 1.4, and 1.7 minimum alveolar concentration isoflurane and halothane on separate days. RESULTS: Chronic rapid pacing increased baseline (sinus rhythm) heart rate, LV end-diastolic pressure, and end-diastolic segment length and decreased mean arterial pressure, LV systolic pressure, and cardiac output. Mw decreased and tau and Kp increased, consistent with LV systolic and diastolic dysfunction. Reductions in dL/dtE/dL/dtA and TVI-E/A occurred, which indicated that LV filling was more dependent on atrial systole. In dogs with cardiomyopathy, isoflurane and halothane increased heart rate and decreased mean arterial pressure, LV systolic pressure, LV end-diastolic pressure, cardiac output, Mw, and Kp. Decreases in LV end-diastolic pressure were more pronounced in dogs anesthetized with 1.1 minimum alveolar concentration isoflurane compared with halothane. Halothane-induced decreases Mw were greater than those observed with equi-minimum alveolar concentration isoflurane. A reduction in tau and increases in TVI-E/TVI-A and the ratio of early to total LV filling were observed with isoflurane. In contrast, halothane caused dose-related reductions in dL/dtE, dL/dtA, TVI-E, and TVI-A, and did not improve the ratios of these variables. CONCLUSIONS: Isoflurane, but not halothane, improved several indices of diastolic performance in dogs with pacing-induced LV dysfunction, despite producing simultaneous negative inotropic effects. These findings can probably be attributed to favorable reductions in LV preload and not to direct lusitropic effects. Improvement of filling dynamics may partially offset the decrement in LV systolic function by isoflurane in the setting of LV dysfunction.

Anesthetics, Inhalation↗
PubMed1996

Mechanism of myocardial protection by isoflurane. Role of adenosine triphosphate-regulated potassium (KATP) channels.

BACKGROUND: The mechanism of the protective actions of volatile anesthetics in ischemic myocardium has not been clearly elucidated. The role of myocardial adenosine triphosphate-regulated potassium (KATP) channels in isoflurane-induced enhancement of recovery of regional contractile function after multiple brief occlusions and reperfusion of the left anterior descending coronary artery (LAD) was studied in dogs anesthetized with barbiturates. METHODS: Dogs (n = 32) were instrumented to measure left ventricular and aortic blood pressure, cardiac output, LAD coronary blood flow velocity, and subendocardial segment length. Regional myocardial perfusion was measured using radioactive microspheres. Hemodynamics and percentage segment shortening (%SS) in the LAD perfusion territory were evaluated after instrumentation was complete; after pretreatment with the KATP channel antagonist, glyburide (0.05 mg/kg-1) or drug vehicle (polyethylene glycol in ethyl alcohol; control experiments); and in the presence or absence of 1 MAC isoflurane administered for 30 min before and during five 5-min occlusions and reperfusion of the LAD in four experimental groups. Isoflurane was discontinued at the onset of the final reperfusion period. Measurements of hemodynamics, %SS, and myocardial perfusion were repeated at several intervals during 180 min after reperfusion of the LAD. RESULTS: Left anterior descending coronary artery occlusion caused regional dyskinesia during each 5-min occlusion in each dog. Control and glyburide-pretreated dogs demonstrated poor recovery of %SS by 180 min after reperfusion (2 +/- 10 and 7 +/- 6% of baseline, respectively). In contrast, dogs anesthetized with isoflurane exhibited complete recovery of function (%SS) by 180 min after reperfusion (82 +/- 8% of baseline). Enhanced recovery of regional contractile function by isoflurane was abolished by pretreatment with glyburide 180 min after reperfusion (16 +/- 10% of baseline). Improvement of functional recovery of stunned myocardium by isoflurane, and the blockade of this action by glyburide, was not associated with changes in hemodynamics or regional myocardial perfusion. CONCLUSIONS: The results indicate that isoflurane prevents decreased systolic shortening caused by multiple episodes of ischemia and reperfusion. These actions result in improved recovery of contractile function of postischemic, reperfused myocardium and are mediated by isoflurane-induced activation of KATP channels.

Adenosine Triphosphate↗
PubMed1996

Differential hemodynamic effects of the nitric oxide donor pirsidomine in comparison to SIN-1, nitroprusside and nitroglycerin.

The systemic and coronary hemodynamic effects of the nitrovasodilator, pirsidomine, were compared with SIN-1, nitroprusside, and nitroglycerin. Four groups consisting of 32 experiments were performed in 17 conscious dogs chronically instrumented for measurement of aortic and left ventricular pressure, left ventricular dP/dtmax, diastolic coronary blood flow velocity, cardiac output, and subendocardial segment length. On separate experimental days, systemic and coronary hemodynamics were recorded during control conditions and after intravenous administration of pirsidomine (1.0, 2.0, and 4.0 mg.kg-1), SIN-1, (50, 100, and 200 micrograms.kg-1), nitroprusside (0.5, 1.0, and 2.0 micrograms.kg-1.min-1), or nitroglycerin (1.0, 2.0, and 4.0 micrograms.kg-1.min-1). Pirsidomine decreased mean arterial, left ventricular systolic and end-diastolic pressures, stroke volume and systemic vascular resistance. Diastolic coronary blood flow velocity and heart rate were increased and coronary vascular resistance decreased by pirsidomine. SIN-1, nitroprusside and nitroglycerin caused similar decreases in preload (evaluated by left ventricular end-diastolic pressure) and afterload (indirectly assessed by mean arterial pressure and systemic vascular resistance) as compared to pirsidomine. However, equihypotensive doses of SIN-1, nitroprusside, and nitroglycerin improved ventricular performance as assessed by increases in left ventricular dP/dtmax, cardiac output and segment shortening, in contrast to those findings during comparable doses of pirsidomine (4 mg.kg-1). Despite similar loading conditions, high doses of pirsidomine did not enhance left ventricular function, suggesting that pirsidomine may have direct negative inotropic effects.

Animals↗
PubMed1995

Dexmedetomidine partially attenuates the sympathetically mediated systemic and coronary hemodynamic effects of cocaine.

The hemodynamic effects of cocaine may be modulated by drugs which interact with central and peripheral adrenoceptors. This investigation examined the systemic and coronary hemodynamic effects of cocaine in conscious dogs with and without premedication with dexmedetomidine (DM). Three groups consisting of 24 experiments were performed using eight dogs chronically instrumented for measurement of aortic and left ventricular pressure, left ventricular dP/dtmax, diastolic coronary blood flow velocity, cardiac output, and subendocardial segment length. On separate experiment days, systemic and coronary hemodynamics were recorded after cocaine (0.5 mg/kg intravenously [I.V.]) with or without DM pretreatment (2 or 4 micrograms/kg I.V.). Cocaine caused increases in heart rate, mean arterial pressure, left ventricular systolic and end-diastolic pressures, dP/dtmax, cardiac output, systemic vascular resistance, and pressure-work index in conscious dogs. Pretreatment with DM attenuated increases in heart rate, dP/dtmax, cardiac output, and pressure-work index produced by cocaine. Systemic vascular resistance increased after the administration of cocaine with and without DM pretreatment; however, systemic vascular resistance remained higher after cocaine in DM-pretreated dogs compared to untreated dogs. Increases in diastolic coronary vascular resistance, but no change in coronary flow velocity, were observed with cocaine alone. In contrast, cocaine increased diastolic coronary blood flow velocity without change in diastolic coronary vascular resistance when administered after DM. The results indicate that increases in heart rate, myocardial contractility, and myocardial oxygen consumption caused by cocaine were attenuated by DM pretreatment. However, cocaine-induced increases in systemic vascular resistance were augmented by DM, suggesting an additive effect at peripheral vascular alpha adrenoceptors.

Adrenergic alpha-Agonists↗
PubMed1995

Modulation of coronary collateral angiogenesis: a canine model of neovascularization induced by chronic ischemia.

Coronary collateral development in response to chronic myocardial ischemia is modulated by the integrated release of a variety of growth factors. Protamine, a specific inhibitor of angiogenesis in vitro and in vivo, may attenuate coronary collateral development. The purpose of this investigation was to characterize a model of canine coronary collateral development and to ascertain the effects of protamine on collateral perfusion in response to chronic myocardial ischemia. Ischemia-induced coronary collateral enhancement in response to daily, repetitive, 2-minute left anterior descending (LAD) coronary artery occlusions over 22 consecutive days was demonstrated in control (saline treated) dogs by time dependent, significant (p < 0.05) increases in collateral blood flow to ischemic myocardium. Concomitant with increases in collateral perfusion, myocardial contractile function during LAD occlusion was progressively normalized, and percent coronary flow repayment was reduced successively. These indicators of collateral development were attenuated significantly by administration of subcutaneous protamine. The present findings demonstrate that a model of brief, repetitive, coronary artery occlusion in chronically instrumented dogs sensitively elicits extensive enhancement of the coronary collateral circulation in response to chronic myocardial ischemia. In contrast, protamine attenuates coronary collateral development through its actions as an inhibitor of angiogenesis.

Animals↗
PubMed1995

Protamine inhibits coronary collateral development in a canine model of repetitive coronary occlusion.

Protamine has been demonstrated to inhibit angiogenesis in vitro and in vivo; however, its effect on coronary collateral development has not been examined. The present investigation tested the hypothesis that subcutaneously administered protamine inhibits canine coronary collateral development in response to chronic myocardial ischemia. Dogs underwent daily, repetitive, 2-min, left anterior descending coronary artery (LAD) occlusions for 22 consecutive days. Regional myocardial blood flow (radioactive microspheres), LAD segment shortening, and coronary flow debt repayment were measured in saline-treated (n = 7) and protamine-treated (n = 6) dogs on days 1, 8, 15, and 22. Coronary collateral development in saline-treated dogs was demonstrated by time-dependent significant (P < 0.05) increases in collateral blood flow to ischemic myocardium [day 1 0.10 +/- 0.01 vs. day 22 0.88 +/- 0.05 (SE) ml.min-1.g-1], progressive normalization of myocardial contractile function during LAD occlusion, and successive reduction in flow debt repayment. In contrast, protamine treatment significantly attenuated, increases in collateral perfusion (day 1 0.13 +/- 0.02 vs. day 22 0.36 +/- 0.03 ml.min-1.g-1). Regional contractile dysfunction and postocclusive reactive hyperemic responses were sustained over time in protamine-treated compared with saline-treated dogs. The results demonstrate that protamine inhibits coronary collateral development in response to chronic myocardial ischemia.

Animals↗
PubMed1995

Impaired microvascular response to graded coronary occlusion in diabetic and hyperglycemic dogs.

The hypothesis that coronary microvascular responses to ischemia are impaired in diabetes was tested in 9 alloxan-treated (60 mg/kg i.v.), 8 hyperglycemic, and 16 control dogs. Arteriolar diameters were measured in intact beating left ventricle by use of stroboscopic epi-illumination and intravital microscopy with fluorescence microangiography. Coronary arterial diameters were measured during graded reductions in mean coronary perfusion pressure to 60 +/- 1 (SE) mmHg (mild stenosis), 39 +/- 1 mmHg (severe stenosis), and 26 +/- 1 mmHg (coronary artery occlusion). Blood glucose levels were 95 +/- 5, 264 +/- 17, and 277 +/- 15 mg/dl in control, diabetic, and hyperglycemic animals, respectively. In control dogs, arteriolar microvessels (< 100 microns) dilated (24 +/- 5, 31 +/- 5, and 26 +/- 6% change in diameter from baseline during mild stenosis, severe stenosis, and coronary occlusion, respectively). Diabetes or hyperglycemia prevented the normal dilatory response and resulted in decreases in microvascular diameter during decreases in perfusion pressure (-2 +/- 3, -4 +/- 3, and -15 +/- 4% change in diameter in diabetic animals and -11 +/- 2, -9 +/- 4, and -8 +/- 5% change in diameter in hyperglycemic animals). Large-vessel (> 100 microns) dilation was also significantly impaired in diabetic and hyperglycemic animals. Myocardial perfusion was significantly lower in the epicardium during a severe stenosis in diabetic and hyperglycemic than in control dogs. Because the ATP-sensitive K+ (KATP) channel mediates this response in normal animals, we tested the hypothesis that KATP channel responsiveness is impaired in diabetes and hyperglycemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Direct negative inotropic and lusitropic effects of sevoflurane.

BACKGROUND: Volatile anesthetics depress left ventricular mechanical performance during multiple phases of the cardiac cycle. The effects of sevoflurane on systolic and diastolic function have yet to be fully evaluated. This investigation characterized the systemic and coronary hemodynamic, inotropic, and lusitropic actions of sevoflurane in chronically instrumented dogs in the presence and absence of autonomic nervous system (ANS) reflexes. METHODS: Because ANS activity may influence the actions of volatile anesthetics in vivo, experiments were conducted in both ANS-intact and ANS-blocked animals. Eighteen experiments were performed in nine dogs chronically instrumented for measurement of aortic and left ventricular pressure, rate of change of left ventricular pressure, subendocardial segment length, diastolic coronary blood flow velocity, and cardiac output. The preload recruitable stroke work slope was used to assess myocardial contractility. Diastolic function was evaluated by a time constant of isovolumic relaxation, maximum segment lengthening velocity during rapid ventricular filling, and a regional chamber stiffness constant. Dogs were assigned to receive sevoflurane with or without pharmacologic blockade of the ANS in a random fashion. On separate experimental days, systemic and coronary hemodynamics and left ventricular pressure--segment length diagrams and waveforms were recorded in the conscious state and during sevoflurane anesthesia (1.0, 1.25, 1.5, and 1.75 MAC). RESULTS: In dogs with intact ANS reflexes, sevoflurane caused significant (P < 0.05) increases in heart rate and dose-related decreases in mean arterial pressure, left ventricular systolic pressure, cardiac output, and diastolic coronary vascular resistance. Sevoflurane also decreased myocardial contractility (preload recruitable stroke work slope 96 +/- 4 in the conscious state to 42 +/- 3 mmHg at 1.75 MAC). Sevoflurane prolonged isovolumic relaxation (time constant of isovolumic relaxation 35 +/- 1 in the conscious state to 51 +/- 3 ms at 1.75 MAC) and decreased rapid ventricular filling (maximum segment lengthening velocity 40.2 +/- 6.0 in the conscious state to 21.8 +/- 3.8 mm.s-1 at 1.75 MAC) without affecting regional chamber stiffness. Sevoflurane caused similar alterations in functional indices of left ventricular systolic and diastolic performance in autonomically blocked dogs. CONCLUSIONS: Sevoflurane caused direct negative inotropic and lusitropic effects in chronically instrumented dogs with and without ANS blockade.

Anesthetics↗
PubMed1994

Perfusion of ischemic myocardium during anesthesia with sevoflurane.

BACKGROUND: Sevoflurane produces direct vasodilation of coronary arteries in vitro and decreases coronary vascular resistance in vivo, pharmacologic properties that may contribute to the development of "coronary steal." This investigation examined the effects of sevoflurane on the distribution of regional myocardial perfusion in chronically instrumented dogs with steal-prone coronary artery anatomy. METHODS: Dogs were chronically instrumented for measurement of aortic and left ventricular pressure, diastolic coronary blood flow velocity and subendocardial segment length. After recovery from surgery, dogs underwent repetitive, brief, left anterior descending coronary artery (LAD) occlusions via an implanted hydraulic vascular occluder to enhance collateral development. A progressive left circumflex coronary artery (LCCA) stenosis was also obtained using an ameroid constrictor. After development of LCCA stenosis, the LAD was totally occluded to produce a model of multivessel coronary artery disease. Systemic hemodynamics, regional contractile function and myocardial perfusion measured with radioactive microspheres were assessed in the conscious state and during sevoflurane anesthesia at 1.0 and 1.5 MAC with and without restoration of arterial blood pressure and heart rate to conscious levels. RESULTS: Total LAD occlusion with simultaneous LCCA stenosis increased heart rate, mean arterial pressure, left ventricular systolic and end-diastolic pressures, end-diastolic segment length, and rate-pressure product in conscious dogs. Subsequent administration of sevoflurane caused dose-related decreases in arterial pressure, left ventricular systolic pressure, double product, and peak rate of increase of left ventricular pressure at 50 mmHg. Perfusion of normal myocardium was unchanged during sevoflurane anesthesia. In contrast, sevoflurane caused dose-dependent decreases in blood flow to myocardium supplied by the stenotic LCCA, which returned to control levels after restoration of heart rate and arterial pressure. No reduction in collaterally derived blood flow to the occluded region was produced by 1.0 or 1.5 MAC sevoflurane. No redistribution of blood flow away from the occluded LAD region to normal or stenotic myocardium occurred during sevoflurane anesthesia. In fact, increases in the ratio of blood flow between occluded and normal zones or occluded and stenotic zones were observed in the subepicardium during 1.5 MAC sevoflurane with maintenance of the heart rate and arterial pressure at conscious levels. CONCLUSIONS: The results demonstrate that sevoflurane does not reduce or abnormally redistribute myocardial blood flow derived from coronary collateral vessels in a chronically instrumented canine model of multivessel coronary artery obstruction.

Anesthesia, Endotracheal↗
PubMedDate not supplied

Changes in passive but not active mechanical properties predict recovery of function of stunned myocardium.

The time course of alterations in active and passive mechanical properties of stunned myocardium during ischemia and throughout reperfusion has not been thoroughly quantified. This investigation tested the hypothesis that the amount of injury as well as the rate and extent of recovery of contractile function in postischemic, reperfused myocardium are directly correlated to changes in regional active and passive elastance and viscosity. A modified viscoelastic Voigt model was employed to quantify myocardial mechanical properties. Left ventricular pressure and segment length (in both ischemic and normal regions) were fit to the model consisting of an active elastic spring in parallel with a viscous damper and a passive elastic spring. The mechanical properties of myocardium from dogs which recovered (> or = 50%) baseline regional contractile function as determined by percent segment shortening (n=7) were compared to those from dogs that did not recover function (n=7). Both groups displayed decreased active elastance in the ischemic region during coronary artery occlusion, and this decrease was maintained in the nonrecovery group. Increases in viscosity of ischemic myocardium were observed in both groups during coronary occlusion but returned to control only in the recovery group. The nonrecovery group demonstrated increased passive elastance in the ischemic region during coronary occlusion and throughout the reperfusion period whereas the recovery group remained unchanged. We conclude that functional recovery of stunned myocardium is directly related to alterations in mechanical properties caused by ischemia and that changes in passive elastance during occlusion may predict the ability of ischemic myocardium to recover contractile function.

Animals↗