Biomedical subjects

S Levitsky

Publications and source records attributed to S Levitsky.

At least 19 recordsLinked to original sources

PubMed1995

Magnesium cardioplegia enhances mRNA levels and the maximal velocity of cytochrome oxidase I in the senescent myocardium during global ischemia.

BACKGROUND: The aged myocardium accumulates significantly more cytosolic calcium [Ca2+]i during ischemia, and functional recovery is more severely compromised as compared with the mature heart. Cardioplegia ameliorates these phenomena. The mechanism by which increased calcium accumulation reduces functional recovery in the senescent myocardium is unknown, but it has been suggested that futile calcium cycling in the mitochondria leading to depletion of ATP stores during normothermic global ischemia may be involved. METHODS AND RESULTS: To investigate the effect of cardioplegia on mitochondrial calcium ([Ca2+]mt) accumulation and the expression of cytochrome oxidase I (COX I) during global ischemia, mitochondria were isolated from mature (age, 15 to 20 weeks) and aged (age > 130 weeks) rabbit hearts after Langendorff perfusion. Five perfused heart groups were investigated: 30 minutes of global ischemia without treatment (control), with potassium (K, 20 mmol/L), magnesium (Mg, 20 mmol/L), or potassium and magnesium (K/Mg) cardioplegia. No significant difference in [Ca2+]mt was evident in mature hearts with any protocol. In aged hearts, [Ca2+]mt was increased in global ischemia but was ameliorated with Mg and K/Mg cardioplegia. COX I mRNA levels in aged hearts were lower in both control and global ischemia but were increased with cardioplegia. Maximal velocities for COX I were significantly increased with Mg cardioplegia both in the mature and the aged myocardium. CONCLUSIONS: K and/or Mg cardioplegia ameliorates [Ca2+]mt accumulation in aged hearts during normothermic global ischemia and increases COX I mRNA levels to a level not significantly different from that found in mature hearts.

Aging↗

PubMed1995

Does cardiopulmonary bypass alone elicit myoprotective preconditioning?

BACKGROUND: Brief episodes of ischemia can precondition myocardium. Ischemic preconditioning (PC) has been proposed as an adjuvant method of improving myocardial protection during cardiac surgery. It is unknown whether CPB without an episode of ischemia generates the PC response. METHODS AND RESULTS: To prove that PC occurs in sheep, groups 1 (non-CPB control) and 2 (non-CPB ischemic PC, three 5-minute episodes of normothermic regional ischemia) were studied. Groups 3 (CPB alone), 4 (CPB-alpha receptor blockade, phentolamine 5 mg/kg), and 5 (CPB-adenosine receptor blockade, 8-sulfophenyltheophylline 5 mg/kg) were placed on CPB for 30 minutes and subsequently weaned. All groups underwent 60 minutes of normothermic regional ischemia and 150 minutes of reperfusion. The area at risk (AR) was delineated by Monastryl blue pigment, whereas the infarct size (IS) was determine by tetrazolium staining. Body mass, left ventricular mass, and AR were not different between groups. Ischemic PC was demonstrated in this ovine model by a 54% reduction of IS relative to AR (group 1 versus group 2, P < .01). CPB alone produced a similar percentage IS reduction without ischemia (group 3 versus group 1, P < .01) that was prevented by either alpha-adrenergic receptor (group 4 versus group 3, P < .01) or adenosine receptor (group 5 versus group 3, P < .01) blockade. CONCLUSIONS: CPB alone appears sufficient to elicit the PC response important for myocardial protection during cardiac surgery. These data suggest that myocardial alpha-adrenergic receptor and adenosine receptor stimulation are involve in initiating CPB-induced PC.

Animals↗

PubMed1995

Pressure and volume loading of the right ventricle have opposite effects on left ventricular ejection fraction.

BACKGROUND: Left ventricular ejection fraction has been reported to be depressed in patients with right ventricular volume overload (RVVO) due to Ebstein's anomaly and uncomplicated atrial septal defect, whereas it is usually preserved in right ventricular pressure overload (RVPO) due to congenital pulmonic stenosis. In the present study, we examined the hypothesis that the differential timing of active displacement of the ventricular septum into the left ventricle in RVPO (end systole) and RVVO (end diastole) results in opposite effects of RVPO and RVVO on left ventricular ejection fraction. METHODS AND RESULTS: Ten patients with severe tricuspid regurgitation after tricuspid valve resection for endocarditis and 10 patients with primary pulmonary hypertension were studied as models of isolated RVVO and RVPO, respectively. Left ventricular ejection fraction, end-diastolic volume, and regional systolic shortening were measured with the use of echocardiographic techniques in these 20 patients and 10 healthy control subjects. In RVPO, despite marked underfilling of the left ventricle relative to the healthy control subjects (end-diastolic volume, 48 +/- 26 versus 77 +/- 20 mL; P < .02), left ventricular ejection fraction was similar to that of the control subjects (56 +/- 5% versus 60 +/- 4%; P = .07) and only 1 of 10 RVPO patients had an ejection fraction of less than 50%. In contrast, in RVVO the left ventricle was volume replete (end-diastolic volume, 84 +/- 26 versus 77 +/- 20 mL; P = NS), but left ventricular ejection fraction was significantly depressed (51 +/- 4% versus 60 +/- 4%, P < .001) compared with the control subjects, and 4 of 10 RVVO patients had an ejection fraction of less than 50%. Analysis of systolic fractional shortening along two perpendicular short-axis diameters and the mutually orthogonal long axis demonstrated isolated augmentation of fractional shortening in the ventricular septal-to-posterolateral free wall dimension in RVPO (47.4 +/- 13.7% versus 34.2 +/- 13.1%, P < .05) and isolated depression of fractional shortening along that same dimension in RVVO (13.7 +/- 11.8% versus 34.2 +/- 13.1%, P < .001) compared with the control subjects. CONCLUSIONS: End-systolic leftward ventricular septal shift in RVPO results in isolated augmentation of systolic shortening in the septal-to-free wall dimension, whereas end-diastolic leftward ventricular septal shift in RVVO results in isolated reduction in systolic shortening in the septal-to-free wall dimension. As a result, despite relative underfilling of the left ventricle in RVPO, resting left ventricular ejection fraction is preserved, whereas ejection fraction is depressed for the volume-replete left ventricle of patients with RVVO.

Adolescent↗

PubMed1995

Does aprotinin increase the myocardial damage in the setting of ischemia and preconditioning?

BACKGROUND: Aprotinin reduces postoperative bleeding in cardiac operations, but its association with perioperative myocardial infarction remains controversial. Ischemic preconditioning is a novel method of myocardial protection. METHODS: To answer whether aprotinin increases postischemic myocardial damage and also to characterize the effect of aprotinin on ischemic preconditioning, four groups of sheep were fully heparinized to keep activated clotting time readings greater than 750 seconds and subjected to 60 minutes of normothermic regional ischemia (diagonal artery occlusion) with 3 hours of reperfusion. Group I was the control with no treatment, group II received aprotinin (1 million KIU load followed by 250,000 KIU/h), group III underwent ischemic preconditioning (three 5-minute intervals of ischemia and reperfusion) before prolonged 1-hour ischemia, and group IV underwent similar ischemic preconditioning and received aprotinin. Area at risk was delineated by monastryl blue pigment, and infarction size by tetrazolium staining. RESULTS: The ratios of weight of area at risk to left ventricular weight and left ventricular weight to body weight were constant between groups. Infarction size to area at risk ratio data demonstrated that aprotinin increases infarction size by 60% (infarction size to area at risk ratio from 52% +/- 10% to 84% +/- 10% for I versus II; p < 0.001). Aprotinin also attenuates the protective effect of ischemic preconditioning (infarction size to area at risk ratio from 25% +/- 4% to 41% +/- 6%; p < 0.001). CONCLUSIONS: In the setting of ischemia, aprotinin increases myocardial damage. If, however, the heart is provided with protective preconditioning, then the deleterious effect of aprotinin may be neutralized. From these data we suggest that aprotinin should not be used routinely in cardiac operations unless extensive blood loss is anticipated, such as in redo open heart operations.

Animals↗

PubMed1995

Myocardial mitochondrial calcium accumulation modulates nuclear calcium accumulation and DNA fragmentation.

BACKGROUND: Previously, we have shown that normothermic global ischemia increases cytosolic calcium accumulation in both the mature and aged heart. Increased nuclear and mitochondrial calcium accumulation was shown to occur in the aged but not the mature heart, and these age-related differences were associated with increased DNA fragmentation and decreased cellular viability only in the aged heart. METHODS: To investigate the relationship between increased mitochondrial and nuclear calcium and DNA fragmentation, mature and aged rabbit hearts were subjected to normothermic global ischemia with and without the addition of ruthenium red to block mitochondrial calcium influx. Cytosolic calcium accumulation was measured in a parallel experiment using fura-2. RESULTS: Ruthenium red ameliorated mitochondrial calcium accumulation and was associated with both decreased DNA fragmentation and decreased nuclear calcium accumulation. CONCLUSIONS: Nuclear calcium accumulation was correlated with increased mitochondrial calcium accumulation but not increased cytosolic calcium accumulation in the aged heart. Modulation of mitochondrion "futile calcium cycling" may be of significance in the modulation of ischemic myocardial injury.

Aging↗

PubMed1995

The rapid expression of myocardial hsp 70 mRNA and the heat shock 70 kDa protein can be achieved after only a brief period of retrograde hyperthermic perfusion.

The induction of heat shock proteins in the myocardium has been suggested as a possible intervention to allow for enhanced cardioprotection. We have postulated that a brief period of retrograde hyperthermic perfusion would be sufficient to induce Hsp 70 mRNA and protein accumulation. To investigate this hypothesis, rat hearts (n = 45) were perfused at 37 degrees C for 30 min, then perfused for 15 min at 42 degrees C, and allowed to recover at 37 degrees C for 120 min. Control hearts (n = 23) were perfused at 37 degrees C continuously. Northern analysis indicated that in hearts treated with a brief period of retrograde hyperthermic perfusion Hsp 70 mRNA levels were increased 2.85 +/- 0.02-fold (P < 0.01) by 10 min, 4.88 +/- 0.94-fold (P < 0.01) by 15 min, 9.19 +/- 0.62-fold (P < 0.001) by 30 min, 9.4 +/- 0.52-fold (P < 0.001) by 60 min, 9.45 +/- 0.57-fold (P < 0.001) by 90 min and 9.66 +/- 0.99-fold (P < 0.001) by 120 min of normothermic recovery as compared to control hearts. Western analysis revealed that the heat inducible Hsp 72 kDa protein was increased 2.37 +/- 0.45-fold (P < 0.01) at 60 min, 2.53 +/- 0.25-fold (P < 0.01) at 90 min, and 2.7 +/- 0.6&-fold (P < 0.01) at 120 min when compared to control hearts. Our results indicate that the induction of the heat shock protein Hsp 70 can be rapidly achieved through retrograde hyperthermic perfusion of the myocardium.

Animals↗

PubMed1995

Blood cardioplegia in the senescent heart.

As an increasingly aged population undergoes cardiac surgery, myocardial protective strategies must address the fundamental differences between adult and senescent myocardium. In a test of the hypothesis that senescent myocardium is less tolerant of cardioplegic arrest, adult (0.5 to 1.0 years) and senescent (6 to 9 years) sheep underwent 55 minutes of hypothermic blood cardioplegic arrest. A 5-minute dose of terminal warm blood cardioplegic solution was administered followed by 30 minutes of vented reperfusion. Left ventricular volume was monitored by means of sonomicrometric crystals in three orthogonal planes. Myocardial function was assessed with the preload recruitable stroke work relationship. Diastolic function was assessed with two techniques: the "stiffness" coefficient (beta), derived from the exponential end-diastolic pressure-volume relationship, and the time constant of isovolumic left ventricular pressure decay (tau). Data were acquired before arrest and after the reperfusion period. Contractility in the adult hearts was well preserved (preload recruitable stroke work: 63.7 +/- 6.1 versus 56.8 +/- 4.1 mJ/beat per milliliter per 100 gm, prearrest versus postarrest, p = not significant). In contrast, senescent heart contractility was poorly preserved (56.8 +/- 4.1 versus 35.4 +/- 4.2 mJ/beat per milliliter per 100 gm, p < 0.025). Early diastolic relaxation (tau) was prolonged in the adult hearts (42.5 +/- 3.3 versus 48.8 +/- 3.5 msec prearrest versus postarrest, p < 0.05), whereas the senescent hearts were essentially unchanged (49.3 +/- 3.1 versus 52.3 +/- 4.5 msec. p = 0.35). Myocardial stiffness (beta) was unchanged in both groups. When compared with adult hearts, contractility in senescent hearts is poorly preserved after cold blood cardioplegic arrest. Active diastolic relaxation, however, is more prolonged in adult hearts. Passive diastolic properties are unchanged in both groups. Because there are specific age-related differences in tolerance to cardioplegic arrest, extrapolation of myocardial protective strategies from studies in adult hearts to elderly patients may not be appropriate.

Aging↗

PubMed1995

Heat-shock gene expression in alcoholic liver disease in the rat is related to the severity of liver injury and lipid peroxidation.

To evaluate the relationship between heat-shock gene expression and the severity of pathologic liver injury and lipid peroxidation in experimental alcoholic liver disease, we used the intragastric-feeding rat model. Six groups of male Wistar rats weighing between 225 and 250 g were fed liquid diets containing different dietary fats (saturated fat, corn oil, and fish oil) and ethanol or dextrose for 1 month. Pathologic injury, mRNA and protein levels of HSP70, microsomal conjugated dienes, and hydrogen peroxide were evaluated at sacrifice. Fish oil-ethanol fed rats developed the most severe injury, while the saturated fat-ethanol group showed no liver injury. The highest levels of HSP70 mRNA were seen in the fish oil-ethanol group. There was no difference in HSP70 protein levels between the groups. The levels of HSP70 mRNA correlated significantly with microsomal conjugated dienes (r = 0.87, P < 0.01) and hydrogen peroxide (r = 0.90, P < 0.01). Increased centrilobular HSP70 expression was seen in rats showing liver injury. The close relationship seen between oxidant stress and HSP70 mRNA but not protein suggest that the binding of HSP70 protein to other damaged proteins reduces free HSP70 protein leading to increased HSP70 expression. HSP70 expression may also be a cellular adaptive response to ethanol-induced oxidative stress.

Animals↗

PubMed1995

Effect of type of dietary fat and ethanol on antioxidant enzyme mRNA induction in rat liver.

We carried out a study to relate the effect of the type of dietary fat and ethanol on antioxidant enzyme mRNA levels in liver in the intragastric feeding rat model. Different types of dietary fat were administered [saturated fat (SE), corn oil (CE) and fish oil (FE)] with ethanol to induce varying severities of liver injury. Ethanol-fed rats were pair-fed with dextrose-fed controls that received isocaloric amounts of dextrose. All animals were killed at 1 month and the following studies were carried out: evaluation of severity of pathologic liver injury, mRNA quantitation for catalase, glutathione peroxidase (GPx), and manganese superoxide dismutase (MnSOD), microsomal conjugated dienes, and hydrogen peroxide. SE animals had no liver injury, FE animals had severe liver injury, and CE animals had moderate liver injury. Ethanol induced GPx mRNA in all dietary groups, with the highest levels seen in the FE group. The pattern of catalase mRNA induction was similar to that of GPx mRNA. In contrast, MnSOD mRNA was decreased compared to controls in animals that developed pathologic liver injury, i.e., CE and FE groups. A positive correlation was seen between conjugated diene levels and GPx mRNA (r = 0.88, P < 0.01) and catalase mRNA. The similar slopes for the relationship between conjugated dienes and catalase in the fish oil and non-fish oil groups indicate that the same degree of lipid peroxidation increases catalase mRNA to a greater degree in fish oil-fed rats. A positive correlation was also seen between catalase mRNA and H2O2 (r = 0.95, P < 0.001).

Animals↗

PubMed1994

Magnesium cardioplegia reduces cytosolic and nuclear calcium and DNA fragmentation in the senescent myocardium.

Previous reports have indicated that the senescent myocardium is less tolerant to surgically induced ischemia and that diminished functional recovery is associated with alterations in cytosolic calcium ([Ca2+]i) accumulation. Recently, increased [Ca2+]i has been suggested to alter nuclear calcium ([Ca2+]n) accumulation. To investigate the relation between [Ca2+]i and [Ca2+]n, we subjected mature and aged rabbit hearts to normothermic global ischemia, either without treatment or after treatment with potassium cardioplegia, magnesium cardioplegia, or a combination of potassium and magnesium cardioplegia. The relation between altered [Ca2+]n and DNA fragmentation was also investigated. Our results indicate that [Ca2+]i was increased during 30 minutes of normothermic global ischemia without treatment in both the mature and aged hearts (p < 0.05). Accumulation of [Ca2+]i during global ischemia was reduced with the use of potassium, magnesium, and a combination of potassium and magnesium cardioplegia (p < 0.05 versus untreated ischemia) in both the mature and aged hearts. Levels of [Ca2+]n were unaffected by global ischemia or cardioplegia in the mature myocardium; however, in the aged myocardium, [Ca2+]n was increased during global ischemia and with potassium cardioplegia and was associated with increased nuclear DNA fragmentation (p < 0.05). The use of magnesium and a combination of potassium and magnesium cardioplegia attenuated [Ca2+]n accumulation and nuclear DNA fragmentation (p < 0.05). Control of [Ca2+]i and [Ca2+]n was associated with enhanced functional recovery during reperfusion. These results indicate that during normothermic ischemia, there is increased [Ca2+]i and [Ca2+]n in the aged myocardium, and increased [Ca2+]n is associated with increased nuclear DNA fragmentation.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1994

Fura 2 determination of [Ca2+]i in isolated perfused heart using R wave-gated electromechanical shutters.

We describe a novel and relatively inexpensive spectrofluorescence system that supplies rapidly alternating wavelengths to either a standard cuvette or an isolated perfused heart. Its use is illustrated by determining changes in cytosolic intracellular Ca2+ concentration ([Ca2+]i) by using the Ca(2+)-sensitive fluorescent dye fura 2 in a rabbit heart preparation. The system uses two precision electromechanical shutters (capable of gating with respect to the electrocardiographic R wave for signal averaging) allowing alternate fura 2 excitation wavelengths (340 and 380 nm) without moving optical components and uses a fiber optic for conducting excitation and collecting epifluorescence. Sample recordings tracing the [Ca2+]i transient in an entire cardiac cycle and in capturing specific isolated regions (diastole and systole) of the cycle are presented. Limitations of this low-cost but easily implemented system are discussed.

Animals↗

PubMed1994

Right ventricular volume overload results in depression of left ventricular ejection fraction. Implications for the surgical management of tricuspid valve disease.

BACKGROUND: Right ventricular volume overload (RVVO) occurring in conditions such as Ebstein's anomaly may result in depression of left ventricular ejection fraction (LVEF). This study tests this hypothesis by measuring LVEF in 10 patients with RVVO due to tricuspid valve resection for isolated tricuspid valve endocarditis and in 10 age-matched healthy persons. METHODS AND RESULTS: When the modified Simpson's rule was applied to echocardiographic images, LVEF for patients with RVVO measured significantly lower than for age-matched healthy subjects (51 +/- 4% versus 60 +/- 4%, P < .0001). Depression of LVEF does not result simply from reduced venous return to the left ventricle, since left ventricular end-diastolic volume was not significantly different between patients with RVVO and age-matched healthy persons (84 +/- 26 versus 77 +/- 20 mL, NS). Possible explanations for the depression in LVEF may relate to the decreased relative contribution of left atrial systole to left ventricular filling (demonstrated by transmitral pulsed Doppler) or to the mechanical effects of ventricular septal paradox (demonstrated by the abnormal leftward ventricular septal flattening and increase in short-axis cavity eccentricity at end diastole, which returns to normal at end systole) in patients with RVVO. CONCLUSIONS: These findings suggest that surgical excision of the tricuspid valve results in isolated RVVO, which creates not only diastolic overload of the right heart but also depression of LVEF.

Adult↗

PubMed1994

Heat-shock protein 70 mRNA is induced by anaerobic metabolism in rat hearts.

BACKGROUND: Both heat-shock protein (HSP) 70 and its mRNA are induced in the ischemic myocardium. The inductor stimuli are, however, not known. Stretch and ischemic metabolic alterations are the two most likely HSP70 inductors. METHODS AND RESULTS: To assess whether anaerobic metabolism induces HSP70 mRNA expression, 61 rat hearts were perfused with Krebs-Henseleit buffer (37 degrees C) in a modified Langendorff apparatus built for rapid switching between pressure-controlled and flow-controlled perfusions. Each heart was initially perfused for 30 minutes at a constant perfusion pressure of 65 mm Hg. Subsequently, separate hearts were perfused at a constant flow of 8, 6, 4, 2, 1, 0.5, or 0 mL/min for 30 minutes using a nonpulsatile pump (n = 5, each perfusion level). Hemodynamic measurements demonstrated a linear correlation between coronary flow and both perfusion pressure and developed pressure (r = .94 and r = .89, respectively; P < .0001 for both comparisons). Diastolic pressure at the end of the perfusions increased only in globally ischemic hearts (34 +/- 3 mm Hg at 0 mL/min versus 5 +/- 1 mm Hg at 8 mL/min; mean +/- SEM, P < .05). The highest lactate release during the 30-minute constant-flow period was observed at a flow level of 4 mL/min (177 +/- 1 versus 71 +/- 8 mumol at 8 mL/min). Creatine kinase release was detected at 2 mL/min (28 +/- 8 mU/mL after 25 minutes of constant flow versus < 8 mU/mL at 4 mL/min). The highest flow level showing cessation of mechanical activity despite pacing of the hearts was at 2 mL/min (2 of 5 hearts). An increased level of HSP70 mRNA expression was found only at 4 mL/min (10-fold increase). Blocking lactate production by substituting glucose with 2-deoxyglucose in the perfusion buffer reduced the HSP70 mRNA level by 44% at 4 mL/min. No increase of HSP/70 was detected (Western blots) at any flow level. CONCLUSIONS: These results indicate that anaerobic metabolism is a strong stimulus for HSP70 transcription and that cessation of anaerobic metabolism in severe ischemia is associated with a shutdown of HSP70 mRNA expression.

Anaerobiosis↗

PubMed1992

Doppler echocardiographic demonstration of the differential effects of right ventricular pressure and volume overload on left ventricular geometry and filling.

To compare the effects of isolated right ventricular pressure and volume overload on left ventricular diastolic geometry and filling, 11 patients with primary pulmonary hypertension, 11 patients with severe tricuspid regurgitation due to tricuspid valve resection and 11 normal subjects were studied with use of Doppler echocardiographic techniques. Right ventricular systolic overload in primary pulmonary hypertension resulted in substantial leftward ventricular septal shift that was most marked at end-systole and early diastole and decreased substantially by end-diastole. Right ventricular diastolic overload after tricuspid valve resection resulted in maximal leftward ventricular septal shift at end-diastole sparing end-systole and early diastole. The early diastolic distortion of left ventricular geometry associated with right ventricular pressure overload resulted in prolongation of isovolumetric relaxation of the left ventricle (129 +/- 39 ms) and a reduction in early diastolic filling compared with values in normal subjects. Late diastolic distortion of left ventricular geometry associated with right ventricular volume overload had no influence on the duration of left ventricular isovolumetric relaxation (52 +/- 32 ms) but caused a reduction in the atrial systolic contribution to late diastolic filling of the left ventricle compared with values in normal subjects. In patients with right ventricular pressure overload, 52 +/- 16% of left ventricular filling occurred in early diastole compared with 78 +/- 11% in patients with right ventricular volume overload (p less than 0.001). The differential effects of systolic and diastolic right ventricular overload on the pattern of left ventricular filling appear to be related to the timing of leftward ventricular septal displacement.

Adult↗

PubMed1992

Preoperative risk factors that predict hospital length of stay in coronary artery bypass patients > 60 years old.

BACKGROUND: The ability to predict prolonged length of stay (LOS) is essential to control escalating hospital costs. Operative mortality is a poor predictor of LOS; morbidity as defined by hospitalization for > 14 days after coronary artery bypass graft surgery (CABG), appears to be responsible for increasing costs. The purpose of this study was to measure preoperative predictive indicators of increased LOS with an eventual plan to offer alternative cost-benefit therapeutic options. METHODS AND RESULTS: Nine hundred twenty-four consecutive patients (age, 60-86 years) undergoing CABG were retrospectively studied by means of the Cox proportional hazards model. Seventeen variables, excluding death, were analyzed and quantified as to importance, and point totals were calculated for each patient. Scores were 12 for congestive heart failure and intra-aortic balloon assist device; 10, creatinine > 2; 6, intra-aortic balloon assist device only; 5, congestive heart failure only; 3, obesity; 6, age > 75 years; 3, age 70-75 years; and 2, 65-69 years. CONCLUSIONS: Increasing index score directly correlated with an exponential increase in LOS. These data substantiate the hypothesis that a mathematical model can predict LOS in CABG patients and may offer rational alternative strategies in delivering cost-effective health care.

Age Factors↗

PubMed1992

Effect of aging on intracellular Ca2+, pHi, and contractility during ischemia and reperfusion.

BACKGROUND: To investigate the effect of aging on myocardial ischemic and reperfusion injury, cytosolic calcium (Ca2+), intracellular pH (pHi), and mechanical performance were measured in isolated perfused rabbit hearts. METHODS AND RESULTS: Hearts of mature (4-5-month-old) and aged (28-38-month-old) rabbits were loaded with 10 microM of fura-2 or 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF) and subjected to 30 minutes of normothermic ischemia and reperfusion. Cytosolic Ca2+ levels ([Ca2+]) during the nonbeating ischemic period and end-diastolic Ca2+ levels ([EDCa2+]) during reperfusion were determined from the fura-2 fluorescence ratio of emission at 510 nm during excitation at 340 and 380 nm. pHi was obtained from the ratio of emission at 530 nm during excitation at 450 and 490 nm. [Ca2+] of the mature group (n = 8) increased from 188 +/- 19 nM (mean +/- SEM) to 373 +/- 32 nM during ischemia, and that of the aged group (n = 7) increased from 242 +/- 17 to 465 +/- 20 nM. The rise of [Ca2+] of the aged group was significantly greater (p < 0.05) than that of the mature group. Immediately after reperfusion, [EDCa2+] in both groups returned to the preischemic level. pHi decreased to the same extent (from 7.2 to 6.7) during ischemia and returned to preischemic values during reperfusion. The mature group recovered 84 +/- 3% of left ventricular peak pressure after ischemia, whereas the aged group recovered only 55 +/- 3% (p < 0.005). Functional recovery was inversely correlated to the increase of [Ca2+] during ischemia (r = 0.66). CONCLUSIONS: Aged hearts exhibit greater accumulation of [Ca2+] during ischemia and less functional recovery after ischemia than mature hearts. The greater rise of [Ca2+] in aged hearts is not a result of the difference of buffering capacity for ischemia-induced acidosis.

Aging↗

PubMed1992

Retrograde is superior to antegrade continuous warm blood cardioplegia for acute cardiac ischemia.

BACKGROUND: Theoretically, the efficacy of continuous warm blood cardioplegia may be improved when administered retrogradely (RCWBC) rather than antegradely (ACWBC) in the setting of acute regional ischemia because of enhanced oxygen and substrate delivery to myocardial tissue distal to an acute coronary artery occlusion. METHODS AND RESULTS: Eighteen Yorkshire swine were instrumented for quantification of global left ventricular systolic, diastolic, and regional left anterior descending coronary artery (LAD) zone mechanics before and after 10 minutes of mid-LAD occlusion, followed by 60 minutes of cardiac arrest using continuous warm blood cardioplegia. Initially, 20 ml/kg of 37 degrees C oxygenated blood cardioplegia (hematocrit, 22 +/- 0.6%) was infused antegradely, followed by maintenance of 75 ml/min ACWBC (n = 9) or 60-100 ml/min of RCWBC (n = 9). LAD occlusion was released 20 minutes after cardiac arrest (30 minutes total LAD ischemia), simulating surgical revascularization. Postischemic recovery of global preload recruitable stroke work was nearly complete with RCWBC but significantly depressed with ACWBC (84.9 +/- 9.5% versus 52.4 +/- 5.1%, respectively; p < 0.01). LAD regional stroke work was also well preserved postischemically with RCWBC but showed no functional recovery and systolic bulging after ACWBC (87.4 +/- 13.7% versus -11.36 +/- 7.46% of control values; p < 0.01). Global diastolic stiffness calculated using the beta-coefficient of an exponential end-diastolic pressure-versus-volume relation was unchanged with ACWBC but increased significantly after RCWBC (from 0.027 +/- 0.002 to 0.028 +/- 0.003 mm Hg/ml and from 0.028 +/- 0.003 to 0.036 +/- 0.004 mm Hg/ml, respectively). CONCLUSIONS: These data suggest that with acute regional ischemia, both global and ischemic zone regional systolic function are depressed by ACWBC, whereas RCWBC affords adequate protection of contractile performance. However, a loss of diastolic compliance may result as a consequence of warm retrograde delivery.

Animals↗

PubMed1992

Age-related differences in cardiac susceptibility to ischemia/reperfusion injury. Response to deferoxamine.

Age-related differences in susceptibility to ischemia/reperfusion injury and the response to the iron chelator deferoxamine during reperfusion were studied in isolated nonworking rabbit hearts subjected to 30 or 40 minutes of ischemia at 37 degrees C followed by 30 minutes of reperfusion. In the experimental group, hearts received a bolus of deferoxamine just before the moment of reflow, followed by a continuous infusion during the first 10 minutes of reperfusion. Isovolumic systolic (peak developed pressure) and diastolic (diastolic pressure versus balloon volume relationship) function was assessed with an intracavity balloon and incremental volume changes. In separate groups of hearts, adenine nucleotide content (adenosine triphosphate, diphosphate, and monophosphate) was measured before ischemia, at end-ischemia, and 30 minutes after reperfusion. The cardiac function measurements showed that after 30 minutes of ischemia and 30 minutes of reperfusion, peak developed pressure in newborn hearts recovered to 89% +/- 5% of preischemic levels; this recovery was significantly better than that of adult hearts, which exhibited 67% +/- 6% (p less than 0.01) recovery. Deferoxamine significantly improved cardiac function only in adult hearts (p less than 0.01). However, after 40 minutes of ischemia and 30 minutes of reperfusion, peak developed pressure in newborn hearts was reduced to 61% +/- 3% and was not significantly better than that of adult hearts (54% +/- 5%). Deferoxamine significantly improved systolic function in both newborn and adult hearts (p less than 0.01) exposed to 40 minutes of ischemia. Myocardial adenosine triphosphate content fell markedly by the end of 30 and 40 minutes of ischemia in both groups. After 30 minutes of ischemia, newborn but not adult hearts were able to completely recover adenosine triphosphate content by 30 minutes of reperfusion. This advantage was lost after 40 minutes of ischemia. Deferoxamine had no effect on recovery of adenosine triphosphate content in any group. We conclude that (1) newborn hearts recover postischemic function and metabolism faster than adult hearts after shorter periods of ischemia; (2) this advantage is lost as the ischemic period is prolonged; (3) deferoxamine improved postischemic cardiac function after longer ischemic periods, in both age groups, but failed to improve the recovery of myocardial adenosine triphosphate content.

Adenine Nucleotides↗