Search PubMed⌕ Search

Biomedical subjects

J R Kersten

Publications and source records attributed to J R Kersten.

At least 37 records · Page 2Linked to original sources
PubMed1999

Sevoflurane reduces myocardial infarct size and decreases the time threshold for ischemic preconditioning in dogs.

BACKGROUND: Recent evidence indicates that volatile anesthetics exert protective effects during myocardial ischemia and reperfusion. The authors tested the hypothesis that sevoflurane decreases myocardial infarct size by activating adenosine triphosphate-sensitive potassium (K(ATP)) channels and reduces the time threshold of ischemic preconditioning necessary to protect against infarction. METHODS: Barbiturate-anesthetized dogs (n = 75) were instrumented for measurement of aortic and left ventricular pressures and maximum rate of increase of left ventricular pressure and were subjected to a 60-min left anterior descending (LAD) coronary artery occlusion followed by 3-h reperfusion. In four separate groups, dogs received vehicle or the K(ATP) channel antagonist glyburide (0.1 mg/kg intravenously), and 1 minimum alveolar concentration sevoflurane (administered until immediately before coronary artery occlusion) in the presence or absence of glyburide. In three additional experimental groups, sevoflurane was discontinued 30 min (memory) before the 60-min LAD occlusion or a 2-min LAD occlusion as an ischemic preconditioning stimulus was used with or without subsequent sevoflurane (with memory) pretreatment. Regional myocardial perfusion and infarct size were measured with radioactive microspheres and triphenyltetrazolium staining, respectively. RESULTS: Vehicle (23 +/- 1% of the area at risk; mean +/- SEM) and glyburide (23 +/- 2%) alone produced equivalent effects on myocardial infarct size. Sevoflurane significantly (P < 0.05) decreased infarct size (13 +/- 2%). This beneficial effect was abolished by glyburide (21 +/- 3%). Neither the 2-min LAD occlusion nor sevoflurane followed by 30 min of memory were protective alone, but together, sevoflurane enhanced the effects of the brief ischemic stimulus and profoundly reduced infarct size (9 +/- 2%). CONCLUSION: Sevoflurane reduces myocardial infarct size by activating K(ATP) channels and reduces the time threshold for ischemic preconditioning independent of hemodynamic effects in vivo.

Adenosine Triphosphate↗
PubMed1998

Cardiovascular effects of verapamil enantiomer combinations in conscious dogs.

We examined the systemic and coronary hemodynamic effects of five combinations of R- and S-verapamil enantiomers (R/S; 100/0, 90/10, 80/20, 50/50, and 20/80%, respectively) in conscious dogs chronically instrumented for measurement of aortic and LV pressure, +dP/dt, subendocardial segment length, coronary blood flow velocity, and aortic blood flow. Dogs received escalating doses (0.1, 0.2, and 0.4 mg kg(-1)) of each verapamil combination over 2 min at 30 min intervals on different experimental days and peak changes in hemodynamics were recorded 2 min after each dose. All verapamil combinations increased heart rate, mean aortic blood flow, and coronary blood flow velocity and decreased calculated systemic and coronary vascular resistance. Alterations in coronary hemodynamics were most pronounced with 20/80 R/S verapamil. Racemic and 20/80 R/S verapamil decreased mean arterial and left ventricular systolic pressure, in contrast to combinations with greater concentrations of the R enantiomer. Left ventricular function was unchanged during administration of 100/0, 90/10, and 80/20 R/S verapamil. Direct negative inotropic and lusitropic effects occurred with 50/50 and 20/80 R/S verapamil. The high dose of 20/80 R/S verapamil also increased left ventricular end-diastolic pressure and the regional chamber stiffness constant, consistent with diastolic dysfunction. The results indicate that combinations of R- and S-verapamil produce differential hemodynamic and left ventricular functional effects in conscious, unsedated dogs that are dependent on the relative ratio of these enantiomers.

Animals↗
PubMed1998

Propofol, but not thiopentone or etomidate, enhances isoflurane-induced coronary vasodilatation in dogs.

PURPOSE: To test the hypothesis that thiopentone, propofol, and etomidate alter the coronary vascular effects of abruptly administered isoflurane. METHODS: Dogs (n = 6) received inspired isoflurane 5% in the presence of thiopentone (20 mg.kg-1 induction dose and 20 mg.kg-1.hr-1 infusion), propofol (5 mg.kg-1 induction dose and 40 mg.kg-1.hr-1 infusion), etomidate (2 mg.kg-1 induction dose and 5 mg.kg-1.hr-1 infusion), or isoflurane (1.0 MAC) anaesthesia in a random fashion. Haemodynamics were assessed in the conscious state, during baseline anaesthesia, and at 30 sec intervals for five minutes after beginning isoflurane 5%. RESULTS: Rapidly administered isoflurane caused greater (P < 0.05) reductions in coronary vascular resistance in thiopentone- or propofol--than in isoflurane-anaesthetized dogs. Isoflurane produced greater (P < 0.05) increases in the ratio of coronary blood flow velocity to pressure-work index (an index of myocardial oxygen consumption; +109 +/- 19% during isoflurane alone vs +182 +/- 27% change from baseline during propofol and isoflurane) consistent with relatively greater direct coronary vasodilatation during baseline propofol than during baseline isoflurane anaesthesia. Isoflurane caused larger increases in coronary blood flow velocity in dogs anaesthetized with etomidate concomitant with higher coronary perfusion pressure and pressure-work index than in those anaesthetized with isoflurane alone. CONCLUSIONS: The results suggest that thiopentone, propofol, and etomidate each uniquely modify the coronary vascular responses to abrupt administration of high inspired concentrations of isoflurane in chronically instrumented dogs.

Anesthetics↗
PubMed1998

A novel alpha 2-adrenoceptor antagonist attenuates the early, but preserves the late cardiovascular effects of intravenous dexmedetomidine in conscious dogs.

OBJECTIVES: To test the hypothesis that L-659,066, a peripherally acting alpha 2-adrenoceptor agonist, will abolish the early pressor response but preserve the late depressor action of intravenous dexmedetomidine in conscious, unsedated dogs. DESIGN: A prospective investigation. SETTING: A laboratory research. PARTICIPANTS: Nine chronically instrumented dogs. INTERVENTIONS: Dogs received dexmedetomidine, 5 micrograms/kg intravenously, in the presence or absence of L-659,066, 0.1, 0.2, or 0.4 mg/kg intravenously, pretreatment in a random fashion determined with a Latin square design on different experimental days. MEASUREMENTS AND MAIN RESULTS: Systemic and coronary hemodynamics were assessed under control conditions, 30 minutes after administration of L-659,066 and 5 and 60 minutes after intravenous administration of dexmedetomidine. Dexmedetomidine alone acutely increased mean arterial pressure (106 +/- 3 to 175 +/- 4 mmHg; p < 0.05), left ventricular (LV) systolic and end-diastolic pressures, systemic vascular resistance (3,400 +/- 350 to 13,360 +/- 2,290 dyne.s.cm-5; p < 0.05), and coronary vascular resistance (2.69 +/- 0.19 to 4.18 +/- 0.43 mmHg.Hz-1.10(-2); p < 0.05) and decreased LV +dP/dtmax and cardiac output (2.6 +/- 0.3 to 1.3 +/- 0.2 L/min; p < 0.05). Dexmedetomidine alone decreased heart rate, mean arterial pressure, and LV systolic pressure and caused sustained reductions in +dP/dtmax and cardiac output up to 60 minutes after administration. L-659,066 alone increased heart rate, +dP/dtmax, cardiac output, and coronary blood flow velocity and decreased systemic vascular resistance. Mean arterial and LV pressures and coronary vascular resistance were unchanged. Pretreatment with L-659,066 abolished the acute dexmedetomidine-induced increases in mean arterial pressure, LV pressures, systemic and coronary vascular resistance and decreases in +dP/dtmax and cardiac output. In contrast, reductions in mean arterial pressure and LV systolic pressure observed 60 minutes after administration of dexmedetomidine were preserved in dogs receiving L-659,066. Cardiac performance, systemic vascular resistance, and coronary hemodynamics were also maintained to a greater degree 60 minutes after dexmedetomidine administration in the presence of L-659,066. CONCLUSION: L-659,066 prevents the immediate pressor effects of 5 micrograms/kg of intravenous dexmedetomidine but preserves the majority of the late beneficial cardiovascular effects of this selective alpha 2-adrenoceptor agonist in conscious dogs.

Adrenergic alpha-Agonists↗
PubMed1998

Etomidate adversely alters determinants of left ventricular afterload in dogs with dilated cardiomyopathy.

UNLABELLED: We tested the hypothesis that etomidate produces similar alterations in left ventricular (LV) afterload in dogs with normal LV function or dilated cardiomyopathy. Dogs were instrumented for LV and aortic pressures, and aortic blood flow. LV afterload was measured with aortic input impedance and quantified with a three-element Windkessel model. In one group of experiments, dogs (n = 6) were paced at 240 bpm for 18 +/- 2 days (mean +/- SEM). Hemodynamic data were recorded in sinus rhythm in the conscious state and during etomidate anesthesia (5, 10, and 20 mg x kg(-1) x h(-1)). Identical experiments were conducted in a separate group of chronically instrumented dogs not subjected to LV pacing (n = 6). No changes in heart rate and arterial and LV pressures were observed during etomidate anesthesia in cardiomyopathic dogs. There were decreases in arterial and LV systolic pressure during the administration of 20 mg x kg(-1) x h(-1) etomidate to dogs with normal LV function. Etomidate significantly (P < 0.05) increased total arterial resistance (R; 3220 +/- 290 dynes x s x cm(-5) during control to 6110 +/- 790 dynes x s x cm(-5) during 10 mg x kg(-1) x h(-1)) and characteristic aortic impedance (Zc; 141 +/- 22 dynes x s x cm(-5) during control to 161 +/- 23 dynes x s x cm(-5) during 20 mg x kg(-1) x h(-1)) and decreased total arterial compliance (C; 0.70 +/- 0.15 mL/mm Hg during control to 0.45 +/- 0.07 mL/mm Hg during 10 mg x kg(-1) x h(-1)) in cardiomyopathic but not healthy dogs. Etomidate markedly reduced mean aortic blood flow (2.26 +/- 0.17 L/min during control to 1.39 +/- 0.20 L/min during 10 mg x kg(-1) x h(-1)) and increased the time constant of LV relaxation (54 +/- 3 ms during control to 74 +/- 9 ms during 20 mg x kg(-1) x h(-1)) in dogs with LV failure. Arterial pressure is maintained during etomidate anesthesia in the presence of LV dysfunction as a result of increases in R and Zc and decreases in C. These deleterious increases in LV afterload further compromise LV systolic and diastolic performance in dogs with dilated cardiomyopathy. IMPLICATIONS: The results of this investigation indicate arterial pressure is maintained during etomidate anesthesia as a consequence of increases in left ventricular (LV) afterload that further diminish LV systolic and diastolic performance in the presence of impaired LV function.

Anesthetics, Intravenous↗
PubMed1998

Cardiovascular effects of propofol in dogs with dilated cardiomyopathy.

BACKGROUND: The authors tested the hypothesis that propofol improves left ventricular diastolic function in dogs with dilated cardiomyopathy by reducing left ventricular preload and afterload. METHODS: Seven dogs were instrumented for left ventricular and aortic pressures, aortic blood flow, and subendocardial segment length. Left ventricular afterload and contractility were quantified with aortic input impedance and preload recruitable stroke work, respectively. Diastolic function was evaluated with a time constant of left ventricular relaxation (tau); segment-lengthening velocities and time-velocity integrals during early left ventricular filling (dL/dtE and TVI-E, respectively) and atrial systole (dL/dtA and TVI-A, respectively); and a regional chamber stiffness constant (K). Dogs were paced at 240 beats/min for 18 +/- 3 days, and hemodynamics were recorded in sinus rhythm in the conscious state. Anesthesia was induced with propofol (5 mg/kg) and maintained with propofol infusions at 25, 50, and 100 mg x kg-1 x h-1, and hemodynamics were recorded after 15 min of equilibration at each dose. RESULTS: Propofol decreased mean arterial pressure, left ventricular end-diastolic pressure, and K but did not change heart rate. Propofol reduced total arterial resistance and increased total arterial compliance derived from aortic input impedance. Propofol also reduced preload recruitable stroke work. The lowest dose of propofol decreased tau. Propofol decreased dL/dtE and TVI-E and reduced the dL/dt-E/A and TVI-E/A ratios. CONCLUSIONS: Propofol reduces left ventricular preload, afterload, and regional chamber stiffness, causes direct negative inotropic effects, and impairs early-diastolic left ventricular filling in dogs with dilated cardiomyopathy.

Anesthetics, Intravenous↗
PubMed1998

Dexmedetomidine produces similar alterations in the determinants of left ventricular afterload in conscious dogs before and after the development of pacing-induced cardiomyopathy.

BACKGROUND: The authors tested the hypothesis that intravenous dexmedetomidine produces alterations in left ventricular (LV) afterload that are deleterious to cardiac performance in conscious dogs with pacing-induced cardiomyopathy. METHODS: Dogs (n = 8) were fitted with instruments for long-term measurement of LV and aortic blood pressure, aortic blood flow, and subendocardial segment length and received dexmedetomidine (1.25, 2.5, and 5 microg/kg) in a cumulative manner before and after 19+/-3 (mean +/- SEM) days of rapid LV pacing. LV afterload was measured with aortic input impedance [Zin(omega)] and quantified with a three-element Windkessel model. Hemodynamics and Zin(omega)) were assessed under control conditions and 5 and 60 min after administration of each dose. RESULTS: Dexmedetomidine caused early and late decreases in heart rate, the maximum rate of increase of LV pressure, mean aortic blood flow, and stroke volume in dogs before and after pacing. Dexmedetomidine caused similar early increases in total arterial resistance and decreases in total arterial compliance in dogs before and after pacing. Early dexmedetomidine-induced increases in resistance and decreases in compliance caused similar reductions in mean aortic blood flow in cardiomyopathic compared with healthy dogs. Resistance and compliance returned to control values, and characteristic aortic impedance decreased late after dexmedetomidine in healthy dogs. In contrast, resistance remained elevated late after dexmedetomidine in dogs with dilated cardiomyopathy. CONCLUSIONS: Dexmedetomidine causes similar alterations in hemodynamics and LV afterload in conscious dogs with and without pacing-induced cardiomyopathy.

Adrenergic alpha-Agonists↗
PubMed1998

Cardiovascular effects of xenon in isoflurane-anesthetized dogs with dilated cardiomyopathy.

BACKGROUND: Clinical interest in xenon has been rekindled recently by new recycling systems that have decreased its relative cost. The cardiovascular effects of xenon were examined in isoflurane-anesthetized dogs before and after the development of rapid left ventricular (LV) pacing-induced cardiomyopathy. METHODS: Dogs (n = 10) were chronically instrumented to measure aortic and LV pressure, LV subendocardial segment length, and aortic blood flow. Hemodynamics were recorded, and indices of LV systolic and diastolic function and afterload were determined in the conscious state and during 1.5 minimum alveolar concentration isoflurane anesthesia alone and combined with 0.25, 0.42, and 0.55 minimum alveolar concentration xenon in dogs with and without cardiomyopathy. RESULTS: Administration of xenon to healthy dogs anesthetized with isoflurane decreased heart rate and increased the time constant (tau) of isovolumic relaxation but did not alter arterial and LV pressures, preload recruitable stroke work slope, and indices of LV afterload. Chronic rapid LV pacing increased the baseline heart rate and LV end-diastolic pressure, decreased arterial and LV systolic pressures, and produced LV systolic and diastolic dysfunction. Administration of xenon to isoflurane-anesthetized, cardiomyopathic dogs did not alter heart rate, arterial and LV pressures, myocardial contractility, and indices of early LV filling and regional chamber stiffness. More pronounced increases in tau were accompanied by increases in total arterial resistance during administration of xenon to isoflurane-anesthetized cardiomyopathic compared with healthy dogs. CONCLUSIONS: The results indicate that xenon produces minimal cardiovascular actions in the presence of isoflurane in dogs with and without experimental dilated cardiomyopathy.

Anesthesia, Inhalation↗
PubMed1998

Acute hyperglycemia abolishes ischemic preconditioning in vivo.

Ischemic preconditioning provides a powerful means to reduce myocardial infarct size in vivo and has been proposed to limit the extent of myocardial infarction in patients. In contrast, hyperglycemia correlates with increases in mortality after acute myocardial infarction. Thus we hypothesized that acute hyperglycemia alters the protection afforded by ischemic preconditioning, and this hypothesis was tested in acutely instrumented dogs subjected to a prolonged (60 min) coronary artery occlusion and 3 h of reperfusion. Ischemic preconditioning was elicited by four 5-min occlusion-reperfusion periods in the presence or absence of an intravenous infusion of 15% dextrose in water to produce acute hyperglycemia (plasma glucose concentration of 300 mg/dl). The dose-dependent effects of hyperglycemia on myocardial infarct size independent of preconditioning stimuli were further evaluated in dogs subjected to increases in plasma glucose concentrations to either 300 or 600 mg/dl. Infarct size (triphenyltetrazolium staining) was 24 +/- 2% of the area at risk in control dogs and was significantly (P < 0.05) decreased by ischemic preconditioning (8 +/- 1%). Modest degrees of hyperglycemia (300 mg/dl) had no effect on infarct size (34 +/- 4%) but abolished the protective effect of ischemic preconditioning (30 +/- 5%). In contrast, profound hyperglycemia (600 mg/dl) increased infarct size (44 +/- 6%). Hemodynamics and coronary collateral blood flow (radioactive microspheres) were similar between groups. Thus acute hyperglycemia adversely modulates myocardial injury in response to ischemia in vivo.

Animals↗
PubMed1998

RSR13, a synthetic modifier of hemoglobin-oxygen affinity, enhances the recovery of stunned myocardium in anesthetized dogs.

RSR13 (2-[4-[[(3, 5-dimethylanilino)carbonyl]methyl]phenoxyl]-2-methylpropr ionic acid) is a synthetic allosteric modifier of oxygen (O2)-hemoglobin affinity that increases O2 release to tissue by allosterically stabilizing deoxyhemoglobin. We tested the hypothesis that RSR13 enhances the functional recovery of stunned myocardium in barbiturate-anesthetized dogs instrumented for measurement of left ventricular (LV) and aortic blood pressure, LV +dP/dtmax and subendocardial segment shortening (%SS) in ischemic [left anterior descending (LAD) coronary artery] and normal (left circumflex coronary artery) zones. The partial pressure of oxygen and the Hill coefficient at 50% saturation (P50 and n50, respectively) were determined in arterial blood samples by multiple point tonometry and nonlinear regression analysis. Coronary collateral blood flow in the LAD zone was quantified with radioactive microspheres. Dogs received intravenous vehicle (0.45% saline) or one of two doses of RSR13 (100 or 150 mg.kg-1 bolus followed by a 0.50 or 0.75 mg.kg-1.min-1 infusion, respectively) in a random manner. All dogs were subjected to five 5-min periods of LAD occlusion separated by 5-min periods of reperfusion and followed by 180 min of final reperfusion during which hemodynamics, %SS, arterial blood gases, P50 and n50 were determined at selected intervals. RSR13 caused no hemodynamic effects and coronary collateral blood flow was equivalent among groups. RSR13 increased P50 (+40 +/- 4% for the high dose) and decreased n50 (-31 +/- 2% for the high dose). LAD occlusion caused regional dyskinesia during each 5-min occlusion. Enhanced recovery of %SS by 180 min after final reperfusion was observed in dogs treated with high-dose RSR13 (47 +/- 9% of base line) but not low-dose RSR13 (10 +/- 18% of base line) or vehicle alone (2 +/- 16% of base line). The results suggest that high-dose RSR13 improves the recovery of stunned myocardium throughout reperfusion in open-chest dogs. These findings may be related to increases in O2 availability to ischemic myocardium resulting from RSR13-induced stabilization of the deoxy form of hemoglobin.

Anesthesia↗
PubMed1997

Temporal dependence of coronary collateral development.

OBJECTIVE: Previous evidence suggests that episodes of myocardial ischemia of sufficient duration and intensity are required to produce coronary collateral development during repetitive coronary occlusion. This investigation tested the hypothesis that coronary collateral development is also temporal-dependent. METHODS: Chronically instrumented dogs (n = 16) were subjected to brief (2 min) left anterior descending coronary artery (LAD) occlusions, once every hour, 8 h a day, for 3 weeks or once every hour, 24 h a day for 1 week. Collateral perfusion (radioactive microspheres), LAD contractile function (ultrasonic crystals), and post-occlusive flow debt repayment (LAD flow probe) were measured during occlusions 1, 55, 105, and 155. RESULTS: Increases (P < 0.05 in subendocardial collateral blood flow to ischemic myocardium, progressive normalization of contractile function during LAD occlusion, and successive reduction in flow debt repayment were observed in dogs receiving occlusions over 3 weeks. In contrast, dogs receiving the same number of coronary occlusions over 1 week demonstrated minimal increases in collateral blood flow, persistent regional contractile dysfunction, and sustained flow debt repayment. CONCLUSIONS: The results demonstrate that LAD collateral development in response to repetitive coronary occlusion requires sufficient time for growth adaptation of the collateral circulation to occur.

Animals↗
PubMed1997

Effects of levosimendan on left ventricular function: correlation with plasma concentrations in conscious dogs.

OBJECTIVES: To test the hypothesis that the hemodynamic and left ventricular functional actions of levosimendan (Orion Pharmaceutica, Espoo, Finland), a new myofilament calcium sensitizer with phosphodiesterase-inhibiting properties, in conscious dogs are correlated with plasma concentrations of the drug measured with reverse-phase, high-performance liquid chromatography. DESIGN: Prospective investigation. SETTING: Research laboratory. PARTICIPANTS: Fifteen chronically instrumented dogs. INTERVENTIONS: On different experimental days, dogs were assigned to receive intravenous levosimendan (12 or 24 micrograms/kg loading dose and 0.2 or 0.4 microgram/kg/min infusion, respectively). MEASUREMENTS AND MAIN RESULTS: Systemic and coronary hemodynamics, left ventricular function, and plasma concentrations were determined at scheduled intervals during and after levosimendan infusions. Levosimendan increased heart rate and cardiac output and decreased left ventricular end-diastolic pressure and systemic vascular resistance. Levosimendan caused dose-related enhancement of left ventricular systolic (increases in regional preload recruitable stroke work slope and +dP/dtmax) and diastolic functions (decreases in the time constant of isovolumic relaxation and regional chamber stiffness). The elimination half-life of levosimendan was 0.76 +/- 0.04 hours. CONCLUSIONS: The hemodynamic actions and left ventricular functional effects of levosimendan correlated closely with plasma concentrations and returned to baseline values within 3 hours after discontinuation of the drug.

Animals↗
PubMed1997

Intracoronary levosimendan enhances contractile function of stunned myocardium.

A decrease in myofilament sensitivity to Ca2+ has been proposed as a mechanism for reversible contractile dysfunction after ischemia and reperfusion. The direct actions of intracoronary myofilament Ca2+ sensitizers on stunned myocardium have not been examined. Barbiturate-anesthetized dogs (n = 9) were instrumented for measurement of left ventricular (LV) and aortic blood pressure, cardiac output, left anterior descending coronary artery (LAD) blood flow velocity, and subendocardial segment length (percent segment shortening [%SS]). Dogs were subjected to five 5-min LAD occlusions interspersed by 5-min reperfusions. Three hours after the final reperfusion, levosimendan (1.5, 3, 6, and 12 microg/min) was administered via an intracoronary catheter. Hemodynamic effects and regional myocardial function were determined under control conditions, during each LAD occlusion and reperfusion, 3 h after final reperfusion, and after 10 min equilibration at each dose of levosimendan. Three hours after the final reperfusion, %SS and the ratio of effective to total regional work were significantly (P < 0.05) decreased, and postsystolic shortening area was increased, consistent with myocardial stunning. In stunned myocardium, intracoronary levosimendan caused dose-dependent increases in %SS (2 +/- 1 at 3 h after reperfusion to 13% +/- 2% during 12 microg/min), abolished postsystolic shortening area, and restored the ratio of effective to total regional work while producing minimum systemic hemodynamic effects.

Animals↗