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J A Crestanello

Publications and source records attributed to J A Crestanello.

13 recordsLinked to original sources
PubMed2000

Opening of potassium channels protects mitochondrial function from calcium overload.

Ischemic preconditioning (IPC) protects myocardium from ischemia reperfusion injury by activating mitochondrial K(ATP) channels. However, the mechanism underlying the protective effect of K(ATP) channel activation has not been elucidated. It has been suggested that activation of mitochondrial K(ATP) channels may prevent mitochondrial dysfunction associated with Ca(2+) overload during reperfusion. The purpose of this experiment was to study, in an isolated mitochondrial preparation, the effects of mitochondrial K(ATP) channel opening on mitochondrial function and to determine whether it protects mitochondria form Ca(2+) overload. Mitochondria (mito) were isolated from rat hearts by differential centrifugation (n = 5/group). Mito respiratory function was measured by polarography without (CONTROL) or with a potassium channel opener (PINACIDIL, 100 microM). Different Ca(2+) concentrations (0 to 5 x 10(-7) M) were used to simulate the effect of Ca(2+) overload; state 2, mito oxygen consumption with substrate only; state 3, oxygen consumption stimulated by ADP; state 4, oxygen consumption after cessation of ADP phosphorylation; respiratory control index (RCI: ratio of state 3 to state 4); rate of oxidative phosphorylation (ADP/Deltat); and ADP:O ratio were measured. PINACIDIL increased state 2 respiration and decreased RCI compared to CONTROL. Low Ca(2+) concentrations stimulated state 2 and state 4 respiration and decreased RCI and ADP:O ratios. High Ca(2+) concentrations increased state 2 and state 4 respiration and further decreased RCI, state 3, and ADP/Deltat. PINACIDIL improved state 3, ADP/Deltat, and RCI at high Ca(2+) concentrations compared to CONTROL. Pinacidil depolarized inner mitochondrial membrane, as evidenced by decreased RCI and increased state 2 at baseline. Depolarization may decrease Ca(2+) influx into mito, protecting mito from Ca(2+) overload, as evidenced by improved state 3 and RCI at high Ca(2+) concentrations. The myocardial protective effects resulting from activating K(ATP) channels either pharmacologically or by IPC may be the result of protecting mito from Ca(2+) overload.

Animals↗
PubMed1999

Bioenergetic effect of liposomal coenzyme Q10 on myocardial ischemia reperfusion injury.

The antioxidant and bioenergetic effects of CoQ10 are well known but its clinical utility is limited by the requirement for enteral administration. A newly developed liposomal CoQ10 (CoQ) is water soluble and capable of intravenous administration. The purpose of this study is to determine the mechanism by which acute administration CoQ protects myocardium from reperfusion (Rp) injury. Rats were pretreated with CoQ 10 mg/kg i.v. 30 min prior to the experiment. Control rats were pretreated with liposome only. Hearts were excised and subjected to equilibration, 25 min of normothermic ischemia and 40 min of Rp on a Langendorff apparatus. At end Rp, CoQ hearts recovered 74 +/- 5% of their DP vs. 50 +/- 9% in control (p < 0.05). Aerobic efficiency was maintained (0.66 +/- 0.02 vs. control, 0.5 +/- 0.04, p < 0.003) and CoQ hearts lost less CK activity vs. control (p < 0.02). PCr and ATP were higher than control (p < 0.05, 0.02, respectively). Results show that i.v. CoQ improves recovery of function, aerobic efficiency, CK activity, and recovery of PCr and ATP after Rp. This suggests that acute administration of liposomal CoQ improves myocardial tolerance to I/R via its role as an antioxidant as well as improving oxygen utilization and high energy phosphate production.

Adenosine Triphosphate↗
PubMed1998

Acute administration of liposomal coenzyme Q10 increases myocardial tissue levels and improves tolerance to ischemia reperfusion injury.

UNLABELLED: The antioxidant and bioenergetic effects of CoQ10 (CoQ) suggest it might be ideal therapy for acute myocardial ischemia. Its utility is limited by the requirement for enteral administration. This study related the administration of a new liposomal suspension of CoQ given intravenously to (1) serum and myocardial [CoQ] and (2) recovery of function, myocardial efficiency, and oxidant injury after cardiac ischemia and reperfusion (I/R). Rats (n = 8/group) were given liposomal CoQ 10 mg/kg iv or placebo (Control), 15 min (C-15), 30 min (C-30), and 60 min (C-60) before (1) measurement of serum and myocardial CoQ or (2) Langendorff perfusion of hearts subjected to 15 min equilibration, 25 min ischemia (37 degrees C), and 40 min reperfusion (RP). Developed pressure (DP) was measured via an intraventricular balloon and coronary flow was measured by a digital flow meter. Myocardial efficiency was defined as DP/MVO2 where MVO2 = microl O2 consumed/min/gram LV. At end RP hearts were assayed for CK, an oxidant sensitive enzyme. Maximum preischemic CoQ levels in serum and myocardium occurred 15 and 30 min after administration, respectively. At end reperfusion, C-30 hearts improved the most, recovering 75 +/- 4% of their preischemic DP while Control recovered only 52 +/- 6% (P < 0.03) as well as maintaining better myocardial efficiency (0.69 +/- 0.02 vs Control, 0.43 +/- 0.05) (P < 0.001). C-15, C-30, and C-60 groups all lost less CK activity after RP vs Control (P < 0.04). CONCLUSION: (1) Serum and myocardial levels of CoQ can be raised acutely by iv liposomal CoQ. (2) Myocardial CoQ levels correlate best with I/R protection. (3) Acute iv CoQ improves function and efficiency and decreases oxidant injury after I/R. Intravenous CoQ may be effective clinically for acute cardiac ischemic syndromes.

Animals↗
PubMed1998

Pyruvate improves myocardial tolerance to reperfusion injury by acting as an antioxidant: a chemiluminescence study.

BACKGROUND: There is indirect evidence that pyruvate improves myocardial tolerance to ischemia by scavenging oxygen radicals during reperfusion. The objectives of this study were to evaluate (1) lucigenin-enhanced chemiluminescence (LEC) as a method to measure oxygen radical (OR) production in vitro and in vivo and (2) the antioxidant effect of pyruvate during myocardial reperfusion. METHODS: LEC was measured in vitro by adding to lucigenin (1) increasing concentrations of H2O2, (2) H2O2 and different concentrations of catalase, and (3) H2O2 plus pyruvate. Isolated rat hearts perfused with Krebs Henseleit-Lucigenin inside a chemiluminescence chamber were subjected to equilibration, ischemia, and reperfusion without (control) or with pyruvate. Developed pressure, contractility, compliance, and chemiluminescence were recorded. RESULTS: In vitro, LEC directly correlated with H2O2 concentrations (r2 = 0.997) and decreased in the presence of catalase or pyruvate. During myocardial reperfusion there was a surge of chemiluminescence that peaked at 4 minutes. Pyruvate decreased the initial reperfusion peak (9.8 +/- 0.3 x 10(3) cpm in pyruvate group vs 12.4 +/- 0.9 x 10(3) cpm in control; p < 0.05) and the total amount of chemiluminescence generated during reperfusion (65.7 +/- 12 x 10(3) in pyruvate group vs 117.1 +/- 8.2 x 10(3) counts in control; p < 0.05). Pyruvate improved recovery of function after ischemia reperfusion. CONCLUSIONS: LEC is a sensitive indicator of H2O2 concentrations and can evaluate the effect of antioxidants in vitro. It is a continuous, sensitive, and direct measurement of OR production in vivo. LEC is ideal for the evaluation of antioxidant interventions and provides direct evidence that pyruvate acts as an antioxidant while improving myocardial function during reperfusion.

Acridines↗
PubMed1997

The mechanisms of coenzyme Q10 as therapy for myocardial ischemia reperfusion injury.

It has been hypothesized that CoQ10 (CoQ) pretreatment protects myocardium from ischemia reperfusion (I/R) injury by its ability to increase aerobic energy production as well as its activity as an antioxidant. Isolated hearts from rats pretreated with either CoQ 20 mg/kg i.m. and 10 mg/kg i.p. or vehicle 24 and 2 h prior to the experiment, were subjected to 15 min of equilibration (EQ), 25 min of ischemia, and 40 min of reperfusion (RP). Developed pressure, +/-dp/dt, myocardial oxygen consumption, and myocardial aerobic efficiency (DP/MVO2) were measured. 31P NMR spectroscopy was used to determine ATP and PCr concentrations. Lucigenin-enhanced chemiluminescence of the coronary sinus effluent was utilized to determine oxidative stress through the protocol. CoQ pretreatment improved myocardial function after ischemia reperfusion. CoQ pretreatment improved tolerance to myocardial ischemia reperfusion injury by its ability to increase aerobic energy production, and by preserving myocardial aerobic efficiency during reperfusion. Furthermore, the oxidative burst during RP was diminished with CoQ. Similarly it was hypothesized that CoQ protected coronary vascular reactivity after I/R via an antioxidant mechanism. Utilizing a newly developed lyposomal CoQ preparation given i.v. 15 min prior to ischemia, ischemia reperfusion was carried out on Langendorff apparatus as previously described. Just prior to ischemia and after RP, hearts were challenged with bradykinin (BK) and sodium nitroprusside (SNP) and change in coronary flow was measured. CoQ pretreatment protected endothelial-dependent and endothelial-independent vasodilation after I/R. We conclude that CoQ pretreatment protects coronary vascular reactivity after I/R via OH radical scavenger action.

Adenosine Triphosphate↗
PubMed1996

Ischemic preconditioning decreases oxidative stress during reperfusion: a chemiluminescence study.

The mechanism responsible for ischemic preconditioning (IPC) is still unknown but may involve the induction of antioxidant enzymes decreasing oxidative stress during subsequent periods of ischemia (I) and reperfusion (RP). The purpose of this study was to determine whether, in fact, an antioxidant mechanism is involved in the protection afforded by IPC. Lucigenin-enhanced chemiluminescence (LEC), a direct, continuous, nondestructive, on-line method was used to monitor the net amount of free oxygen radicals (FOR) produced during perfusion of rat hearts. Isolated rat hearts were perfused inside a chemiluminescence chamber with lucigenin (1 x 10(-5) M) and subjected to either: (a) 80 min of equilibration (EQ80 group, n = 6), (b) 15 min of EQ, 2 min of IPC, 10 min of reequilibration (REQ), 25 min of I, and 28 min of RP (IPC group, n = 8), or (c) 27 min of EQ, 25 min of I, and 28 min of RP (CTRL, n = 7). Chemiluminescence was measured as counts per minute (cpm) and expressed as %EQ15 (mean +/- SEM). Paired and nonpaired t tests were used for statistical evaluation. EQ80 showed no changes in oxidative stress throughout perfusion (4.5 +/- 0.2 x 10(3) cpm at EQ15 vs 5.1 +/- 0.5 x 10(3) cpm at EQ80, P = NS). During REQ (after IPC) there was a surge of chemiluminescence in IPC hearts compared with CTRL (130 +/- 8% vs 108 +/- 4%, P < 0.05). During reperfusion there was a surge of chemiluminescence in CTRL hearts that was diminished in the IPC hearts (550 +/- 50% vs 380 +/- 50% in IPC, P < 0.05). We conclude that: (1) IPC induces an oxidative stress generating FOR during REQ, (2) IPC decreases the initial FOR burst during RP. We speculate that IPC increases cellular antioxidant defenses which result in decreased oxidative stress during early RP.

Acridines↗
PubMed1996

Elucidation of a tripartite mechanism underlying the improvement in cardiac tolerance to ischemia by coenzyme Q10 pretreatment.

Coenzyme Q10, which is involved in mitochondrial adenosine triphosphate production, is also a powerful antioxidant. We hypothesize that coenzyme Q10 pretreatment protects myocardium from ischemia reperfusion injury both by its ability to increase aerobic energy production and by protecting creatine kinase from oxidative inactivation during reperfusion. Isolated hearts (six per group) from rats pretreated with either coenzyme Q10, 20 mg/kg intramuscularly and 10 mg/kg intraperitoneally (treatment) or vehicle only (control) 24 and 2 hours before the experiment were subjected to 15 minutes of equilibration, 25 minutes of ischemia, and 40 minutes of reperfusion. Developed pressure, contractility, compliance, myocardial oxygen consumption, and myocardial aerobic efficiency were measured. Phosphorus 31 nuclear magnetic resonance (31P-NMR) spectroscopy was used to determine adenosine triphosphate and phosphocreatine concentrations as a percentage of a methylene diphosphonic acid standard. Hearts were assayed for myocardial coenzyme Q10 and myocardial creatine kinase activity at end equilibration and at reperfusion. Treated hearts showed higher myocardial coenzyme Q10 levels (133 +/- 5 micrograms/gm ventricle versus 117 +/- 4 micrograms/gm ventricle, p < 0.05). Developed pressure at end reperfusion was 62% +/- 2% of equilibration in treatment group versus 37% +/- 2% in control group, p < 0.005. Preischemic myocardial aerobic efficiency was preserved during reperfusion in treatment group (0.84 +/- 0.08 mm Hg/(microliter O2/min/gm ventricle) vs 1.00 +/- 0.08 mm Hg/(microliter O2/min/gm ventricle) at equilibration, p = not significant), whereas in the control group it fell to 0.62 +/- 0.07 mm Hg/(microliter O2/min/gm ventricle, p < 0.05 vs equilibration and vs the treatment group at reperfusion. Treated hearts showed higher adenosine triphosphate and phosphocreatine levels during both equilibration (adenosine triphosphate 49% +/- 2% for the treatment group vs 33% +/- 3% in the control group, p < 0.005; phosphocreatine 49% +/- 3% in the treatment group vs 35% +/- 3% in the control group, p < 0.005) and reperfusion (adenosine triphosphate 18% +/- 3% in the treatment group vs 11% +/- 2% in the control group, CTRL p < 0.05; phosphocreatine 45% +/- 2% in the treatment group vs 23% +/- 3% in the control group, p < 0.005). Creatine kinase activity in treated hearts at end reperfusion was 74% +/- 3% of equilibration activity vs 65% +/- 2% in the control group, p < 0.05). Coenzyme Q10 pretreatment improves myocardial function after ischemia and reperfusion. This results from a tripartite effect: (1) higher concentration of adenosine triphosphate and phosphocreatine, initially and during reperfusion, (2) improved myocardial aerobic efficiency during reperfusion, and (3) protection of creatine kinase from oxidative inactivation during reperfusion.

Animals↗
PubMed1996

Coenzyme Q10 protects coronary endothelial function from ischemia reperfusion injury via an antioxidant effect.

BACKGROUND: Cardiac ischemia reperfusion (I/R) injury causes coronary vascular dysfunction. Coenzyme Q10 (CoQ), which preserves cardiac mechanical function after I/R, recently has been recognized as a free radical scavenger. We hypothesized that CoQ protects coronary vascular reactivity after I/R via an antioxidant mechanism. METHODS: Rats were pretreated with either CoQ (20 mg/kg intramuscular and 10 mg/kg intraperitoneal [CoQ group]) or a vehicle (Control) before the experiment. Isolated perfused rat hearts were subjected to 25 minutes of global normothermic ischemia and 40 minutes of reperfusion. The reperfusion-induced oxidative burst was directly assessed by lucigenin enhanced chemiluminescence. Coronary flow was measured at equilibration and after reperfusion with or without bradykinin, an endothelium-dependent vasodilator, and sodium nitroprusside (SNP), an endothelium-independent vasodilator. The effect of intracoronary infusion of hydrogen peroxide (H2O2 0.1 mumol/gm body weight given over 5 minutes), simulating the free radical burst after I/R, also was evaluated. RESULTS: I/R decreased the bradykinin-induced change in coronary flow (-5% +/- 4% versus 26% +/- 3% at equilibration; p < 0.05) and the SNP-induced change (+20% +/- 6% versus +56% +/- 5% at equilibration; p < 0.05). The coronary vasculature after H2O2 infusion revealed a similar loss in vasodilatory responsiveness (+4% +/- 4% in response to bradykinin, +35% +/- 8% in response to SNP; p < 0.05 versus equilibration). Pretreatment with CoQ improved BK-induced vasorelaxation after I/R (+12% +/- 2%; p < 0.05 versus control I/R) or H2O2 infusion (18% +/- 4%; p < 0.05 versus control I/R) but failed to improve SNP-induced vasorelaxation. The CoQ pretreatment decreased the I/R-induced maximal free radical burst (9.3 +/- 0.8 x 10(3) cpm versus 11.5 +/- 1.1 x 10(3) cpm; p < 0.05) during the early period of reperfusion. CONCLUSIONS: Endothelium-dependent vasorelaxation is more sensitive than endothelium-independent relaxation to I/R injury. Via a direct antioxidant effect, CoQ preserved endothelium-dependent vasorelaxation by improving tolerance to I/R injury.

Acridines↗
PubMed1995

The cumulative nature of pyruvate's dual mechanism for myocardial protection.

Pyruvate (PYR) supplementation protects myocardium from ischemia reperfusion injury. This study was designed to characterize and quantify the mechanism underlying this protection: specifically whether this ability resides in PYR's metabolic effect or in its antioxidant effect. Isolated perfused rat hearts (n = 6/group) were subjected to 15 min of equilibration (EQ), 25 min of ischemia, and 10 min of reperfusion (RP). Glucose was the sole metabolic substrate (Control) or was supplemented with PYR (5 mM) during (a) EQ only (PYREQ group), (b) RP only (PYRRP group), or (c) EQ and RP (PYREQ-RP group). Left ventricular developed pressure (DP) and +/- dP/dt were recorded throughout the experiment. ATP concentrations and intracellular pH were determined by 31P NMR spectroscopy. Myocardial creatinine kinase (CK) activity was assayed at end EQ and end RP. In vitro, purified CK was assayed and, after exposure to H2O2 (200 microM) and increasing concentrations of PYR (0-6 mM) for 10 min, reassayed to determine the antioxidant effect of PYR. In all cases PYR improved recovery of mechanical function at end RP (DP: Control, 11 +/- 1%; PRYRP, 23 +/- 6%; PYREQ, 34 +/- 8%; PRYEQ&RP, 53 +/- 7%; P < 0.05 between all groups and Control). Ischemic contracture was delayed in hearts that received PYR during EQ (PYREQ and PYREQ&RP: 17.8 +/- 0.2 vs 12.5 +/- 0.3 min, P < 0.001). PYR during EQ (PYREQ and PYREQ&RP) led to higher end ischemic ATP levels (32 +/- 4% vs 14 +/- 3%, P < 0.001) and a more acidic end ischemic pH (5.92 +/- 0.02 vs 5.98 +/- 0.03 in Control and PYRRP, P < 0.05). PYREQ&RP showed the highest end reperfusion ATP levels (55 +/- 7% vs 38 +/- 4%, P < 0.05 vs other groups).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1995

Nitric oxide as a positive inotropic agent in isolated rat hearts.

The purpose of this study was to examine the inotropic effects of nitroprusside (NP), a direct nitric oxide (NO) donor, in isolated rat hearts. Langendorff-perfused hearts (n = 5), paced at 6 Hz, were subjected to 15 min of equilibration (EQ) followed by infusion of NP, producing a coronary artery concentration of 1 x 10(-5) M. Coronary flow, left ventricular developed pressure (DP), end-diastolic pressure, and contractility and compliance (+/- dP/dt) were monitored throughout the experiment by a computerized data acquisition system. Myocardial oxygen consumption (MVO2) was measured at the end of EQ and after 2 1/2 min of NP infusion. Myocardial efficiency was calculated as the quotient of DP divided by MVO2. Values are expressed as the mean +/- SEM. Paired t tests were used to calculate statistical significance. Values for parameters monitored at end EQ and at 2 1/2 min NP infusion showed that there was a 93% increase in coronary flow, 18, 17, and 16% increases in developed pressure, contractility, and compliance, respectively, no significant change in end-diastolic pressure, a 49% increase in myocardial oxygen consumption, and a 21% decline in myocardial efficiency (P < 0.05 for all differences). We conclude that in the isolated rat heart, NO behaves as a positive inotrope.

Animals↗
PubMedDate not supplied

Uniform safety of beating heart surgery using the octopus tissue stabilization system.

BACKGROUND AND PURPOSE: Minimally invasive coronary artery bypass grafting (CABG) has been facilitated by the introduction of the Octopus Tissue Stabilization system (OTS). OTS improves exposure immobilizing the heart with minimal hemodynamic effects allowing multivessels off cardiopulmonary bypass (CPB) CABG. The purpose of this study was to compare the utilization and clinical outcome of the OTS in three geographically distinct centers. METHODS: 239 patients who underwent OTS-CABG at Allegheny University Hospital/Medical College of Pennsylvania, Harrisburg Hospital, and Park Nicollet Clinic/HealthSystem Minnesota were reviewed. Age, acuity of patients, and number and type of vessels bypassed were recorded. Complications, mortality, length of hospital stay, incidence of conversion to CPB and blood transfusions, and operating room costs were compared to risk matched control patients who underwent CPB CABG during the same period. RESULTS: Results were similar in all three centers. The average age was 62.3 years. Emergent operation was necessary in 7%-10% of patients, the operations averaged 1.8 grafts/patient. Arteries bypassed were LAD, DIAG, OM, RCA, PDA, and RPLB. There were 96% of operations completed without CPB. Morbidity was low (12%). Atrial fibrillation and blood transfusion rate were decreased. Mortality was 0 compared with a predicted mortality of 1.6%. Hospital length of stay was shorter and operating room costs were 61% lower. CONCLUSIONS: OTS provides predictable reproducible immobilization allowing the performance of single and multiple off-pump CABG to almost all coronary branches with minimal morbidity and decreased costs in a variety of patients. Similar findings from three different centers suggests that these results are easily reproducible.

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