PubMed Health⌕ Search

Biomedical subjects

I B Krukenkamp

Publications and source records attributed to I B Krukenkamp.

At least 19 recordsLinked to original sources
PubMed2002

Free emboli formation in the wake of bi-leaflet mechanical heart valves and the effects of implantation techniques.

The high incidence of thromboembolic complications of mechanical heart valves (MHV), primarily due to platelet activation by contact with foreign surfaces and by non-physiological flow patterns past the valve, still limits their success as permanent implants. The latter include elevated shear and turbulent stresses and shed vortices formed in the wake of the valve's leaflets during the deceleration phase, potentially entrapping activated and aggregated platelets. It is hypothesized that these flow patterns induce the formation of free emboli which are the source of cerebrovascular microemboli associated with MHV. Implicit to this hypothesis is that free emboli formation will be affected by the implantation technique employed and the valve orientation, as those will alter the flow characteristics past the valve and the interaction of the platelets with the flow. In this study, numerical simulations of turbulent pulsatile flow past a St. Jude Medical bi-leaflet MHV were conducted. Platelet shear histories were calculated along pertinent turbulent platelet trajectories, and the effect of a misaligned valve on platelet activation was quantified and compared to that of an aligned valve. It demonstrated that the combination of a tilted valve and subannularly sutured pledgets had an explicit detrimental effect on platelet activation, with the following entrapment of the platelets within the shed vortices of the wake leading to a significant increase of the thromboembolic potential of the valve. This numerical model depicted a viable course for free emboli formation, and indicated how the implantation technique may enhance the risk of cardioembolism.

Aortic Valve↗
PubMed2001

Computer aided speckle interferometry: a technique for measuring deformation of the surface of the heart.

An investigation of the inhomogeneous and anisotropic properties of myocardium necessitates a whole field measurement technique with high spatial resolution. Computer aided speckle interferometry (CASI) may be applied to measuring deformation on the epicardial surface of the heart. Silicone carbide particles (approximately 40 microm in diameter) were sprinkled randomly onto the epicardial surface of isolated rabbit hearts. When illuminated with white light, speckles may be observed with a charge coupled device (CCD) camera. A balloon was placed in the left ventricle to control the intracavitary load on the arrested heart. To compare CASI to the "gold" standard technique of sonomicrometry, two ultrasonic transducers were implanted into the wall of the myocardium. Three hearts were exposed to various loading conditions, and at each condition speckle images were recorded. CASI was used to determine the distribution of displacement vectors (both direction and magnitude) in the region imaged by the CCD camera. Strain along the axis of the implanted transducers was determined with CASI and compared to that obtained with sonomicrometry. Strain determined from CASI and sonomicrometry produced equivalent results. Unlike sonomicrometry, whereby the displacement between two points with a relatively large gauge length is obtained, CASI is able to determine displacement vectors for hundreds of "points" within the same region. In conclusion, CASI produced equivalent results to those obtained from sonomicrometry (although not with the same temporal resolution), but it is a whole field deformation mapping technique that has a spatial resolution three orders of magnitude higher than that of sonomicrometry.

Animals↗
PubMed2000

Ischemic but not pharmacological preconditioning requires protein synthesis.

BACKGROUND: Ischemic preconditioning (IPC) and pharmacological preconditioning (PPC) have both been shown to confer cardioprotective effects. However, the role of protein synthesis in preconditioning is unclear. METHODS AND RESULTS: Isolated rabbit hearts were treated with cycloheximide (CHx, 10 micromol/L), a protein synthesis inhibitor at the translational level, before 2 cycles of IPC (5 minutes of global ischemia/5 minutes of reperfusion, n=6) or PPC by pinacidil (PIN, 10 micromol/L; n=6), an ATP-sensitive potassium channel opener. Six rabbit hearts received actinomycin D (Act D, 20 micromol/L; n=6), a protein synthesis inhibitor at the transcriptional level, before IPC. The left anterior descending coronary artery was then occluded for 60 minutes and reperfused for 120 minutes. Control hearts received no treatment before prolonged ischemia (n=6). Left ventricular pressure, action potential duration, and coronary flow were measured. Infarct size is expressed as a percentage of the area at risk. IPC (n=6) and PIN (n=8) hearts experienced reduced infarct size compared with control hearts (22+/-3% and 27+/-2% versus 46+/-3%, IPC and PIN versus control; P:<0.01). Translational blockade (CHx) reversed the IPC infarct size reduction effect (22+/-3% versus 48+/-4%, IPC versus CHx+IPC; P:<0.01) but not the effects of pinacidil (27+/-2% versus 29+/-3%, PIN versus CHx+PIN; P:=NS). Transcriptional blockade (Act D) did not abolish the IPC effect (23+/-5% versus 22+/-3%, Act D+IPC versus IPC; P:=NS). There were no significant differences in electromechanical function consequent to CHx and Act D treatment. CONCLUSIONS: These findings suggest an important role for protein synthesis in the mechanism for IPC-mediated protection at the translational level, which may be different from PPC.

Action Potentials↗
PubMed2000

The role of nitric oxide, K(+)(ATP) channels, and cGMP in the preconditioning response of the rabbit.

BACKGROUND: The role of nitric oxide (NO), K(+)(ATP) channels, and cyclic GMP (cGMP) in preconditioning is unknown. MATERIAL AND METHODS: Isolated rabbit hearts were pretreated with the NO precursor L-arginine (L-Arg), both alone and after infusion of the NO synthetase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME). Guanylate cyclase inhibitor methylene blue (MB) was infused prior to L-Arg in a separate group of hearts. To contrast the mechanisms of NO preconditioning and potassium channel opener (PCO) preconditioning, we infused the PCO pinacidil after L-NAME and the PCO blocker glibenclamide before L-Arg. Control hearts had no drug infused. The LAD coronary artery was occluded for 1 h and reperfused for 1 h in all hearts. Action potential duration (APD(50)), coronary flow (CF), and left ventricular developed pressure (DP) were measured, and infarct size (IS) was determined and expressed as a percentage of the area at risk. RESULTS: L-Arg prolonged APD(50) at 60 min of reperfusion (94 +/- 6 ms vs 69 +/- 2 ms (control) vs 70 +/- 2 ms (L-NAME) vs 74 +/- 3 ms (MB), P < 0.05). L-Arg reduced IS compared with control (24 +/- 2% vs 49 +/- 3%, P < 0.05); this was reversed by either L-NAME (53 +/- 4%, P < 0.05) or MB (43 +/- 3%, P < 0.05), but not by glibenclamide (20 +/- 4%), unlike the increase in CF during L-Arg infusion, which was blocked by glibenclamide. Pinacidil infusion decreased IS (26 +/- 2%), but this effect was blocked by L-NAME (53 +/- 7%, P < 0.05 vs pinacidil), although L-NAME did not blunt the increase in CF. There were no significant differences in DP among groups. CONCLUSION: L-Arginine preconditions the heart through NO generation, and this response is mediated through a cGMP-dependent mechanism, but is independent of the K(+)(ATP) channels. Coronary vasodilation is mediated through a mechanism different from that responsible for cardiomyocyte preconditioning.

Action Potentials↗
PubMed2000

Preconditioning with PKC and the ATP-sensitive potassium channels: a codependent relationship.

BACKGROUND: Both potassium channel openers and protein kinase C have been shown to independently elicit the myoprotective preconditioning response. However, the in vivo dependency between the two is unknown. METHODS: Thirty-seven sheep were divided into seven groups; animals received no pretreatment, pinacidil, pinacidil and potassium channel opener blocker glibenclamide, protein kinase C activator 4beta-phorbol-12,13-dibutyrate (PDBu), or PDBu and protein kinase C blocker chelerythrine. The last two groups underwent opposite blockade, chelerythrine + pinacidil, or glibenclamide + PDBu. All groups underwent 60 minutes of regional ischemia followed by 180 minutes of reperfusion. Regional function was assessed throughout the experiment, and at the conclusion of the study the infarct size (as a percentage of the area at risk) was determined. RESULTS: Infarct size decreased in the groups receiving only pinacidil or PDBu (control: 54%+/-3%, pinacidil: 25% +/-2%, PDBu: 21%+/-3%; p<0.05 pinacidil or PDBu versus control). This preconditioning protection was lost when the direct blocker was given (58%+/-5%, glibenclamide + pinacidil; 70%+/-6%, chelerythrine + PDBu; p = not significant versus control). The preconditioning response was again attenuated when the opposite blockers were given (64%+/-5%, chelerythrine + pinacidil; 63%+/-1%, glibenclamide + PDBu; p = not significant versus control). There was no significant difference in regional function. CONCLUSIONS: This study shows that both protein kinase C and potassium channels are necessary and codependent for preconditioning in the in vivo heart.

Animals↗
PubMed2000

Pharmacological preconditioning with the adenosine triphosphate-sensitive potassium channel opener pinacidil.

BACKGROUND: Ischemic preconditioning (IPC) decreases infarct size after global or regional ischemia. Potassium channel openers also precondition but are subject to dose-limiting vasodilation. We compared the mechanical and electrophysiological effects of ischemic and pharmacological preconditioning in an isolated rabbit heart model. METHODS: Rabbit hearts were preconditioned with either 10 micromol/L pinacidil alone (P-), 10 micromol/L pinacidil with 10 micromol/L phenylephrine (P+), or two cycles of global ischemia and reperfusion (IPC) before 1 hour of LAD occlusion. Left ventricular pressure, epicardial monophasic action potential duration (APD) and coronary flow were monitored throughout. Infarct size was determined at the end of reperfusion. RESULTS: Regional ischemia uniformly decreased APD (p<0.05). During reperfusion, APDs were prolonged beyond preischemic values in all preconditioned groups (p<0.05). P- and P+ reduced the incidence of fibrillation. P- significantly increased coronary flow (+15%, p = 0.001), whereas IPC and P+ did not. However, IPC and P- significantly decreased systolic function (p<0.05) but P+ did not. In addition, IPC depressed diastolic function (p<0.05) but P- and P+ did not. Infarct size was reduced by all methods (p<0.05). CONCLUSIONS: Pinacidil presents a safe and effective alternative to IPC for preserving the heart during regional ischemia. Its coronary vasodilatory effects are safely and effectively reversed by the addition of phenylephrine.

Action Potentials↗
PubMed2000

Amrinone preconditioning in the isolated perfused rabbit heart.

BACKGROUND: Ischemic preconditioning (IPC) reduces infarct size in experimental preparations. IPC, however, is not without detrimental effects. We studied amrinone as a possible alternative to IPC. METHODS: Isolated perfused rabbit hearts were given a 5-minute infusion of 10 micromol/L amrinone followed by a 5-minute washout (n = 6). The anterior descending artery was then occluded for 1 hour and reperfused for 1 hour. Six hearts underwent IPC, with two episodes of 5-minute global ischemia followed by 5-minute reperfusion before LAD occlusion; eight control hearts received no preconditioning. Left ventricular pressure and ischemic zone epicardial monophasic action potentials were continuously monitored. RESULTS: IPC but not amrinone reduced peak pressure before anterior descending artery occlusion. Peak pressure fell significantly during ischemia and reperfusion in all hearts. End diastolic pressure rose significantly during reperfusion in control and IPC hearts but not in amrinone hearts. Action potentials shortened during ischemia in all hearts. They returned to preocclusion values in control hearts but lasted beyond preocclusion values in IPC and amrinone hearts. Both the incidences of ventricular fibrillation and infarct size were significantly reduced in amrinone hearts but not in IPC hearts. CONCLUSIONS: Amrinone is not only a useful inotropic agent but is also a superior preconditioning agent when compared to IPC.

Action Potentials↗
PubMed2000

Functional assessment of disease-free saphenous vein grafts at redo coronary artery bypass grafting.

BACKGROUND: Reoperations for coronary artery bypass grafting are on the rise. The general rule of replacing all saphenous vein grafts (SVGs) older than 5 years of age at the time of reoperation has recently been challenged on clinical grounds. This study provides functional data of endothelial behavior in long-term vein grafts. METHODS: Previously placed SVGs were removed at the time of redo operations. Nitric oxide (NO) measurements in real time were carried out before and after stimulation with morphine. The measurements were compared to the angiographic appearance of the grafts obtained prior to operation. Grafts were categorized into 3 groups: disease-free, moderately diseased, and severely diseased. RESULTS: Sixteen grafts were analyzed. Five were angiographically disease-free, 4 had moderate, and 7 severe disease. In the disease-free group, peak NO production after 10(-6) mol/L morphine stimulation was 35 mol/L, equivalent to the production of native saphenous vein. The severely diseased group did not demonstrate an increase in NO production, and the moderately diseased group produced a small rise in production. CONCLUSIONS: Measurement of NO release of old SVGs, when angiographically pristine, equals that of native saphenous vein. These findings support the recent clinical observations that long-term angiographically disease-free vein grafts are biologically privileged.

Aged↗
PubMed1999

Nitric oxide-generating beta-adrenergic blocker nipradilol preserves postischemic cardiac function.

BACKGROUND: Preconditioning protects the heart from ischemic injury, but some of its effects are reversed by beta-adrenergic blockade. We hypothesize that because nitric oxide is known to precondition the heart, the nitric oxide-generating beta-blocker nipradilol may simultaneously precondition and provide clinically relevant beta-blockade. METHODS: Isolated, crystalloid-perfused rabbit hearts underwent 1 hour of left anterior descending coronary artery ischemia followed by 1 hour of reperfusion. Before ischemia, six hearts received nipradilol, six received the nitric oxide donor L-arginine, four hearts received the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester before L-arginine, nine underwent ischemic preconditioning, and six received beta-blockade by esmolol before ischemic preconditioning. Seven hearts received no pretreatment (control). Action potential duration and ventricular pressure were measured. Infarct size was determined at the end of reperfusion. RESULTS: Both L-arginine and ischemic preconditioning prolonged action potential duration significantly at 60 minutes of reperfusion. Compared with control, infarct size was reduced by ischemic preconditioning (26%+/-4% versus 49%+/-3%, IPC versus control; p<0.01), L-arginine (24%+/-2%; p<0.01 versus control), and nipradilol (24%+/-2%; p<0.01 versus control). Only nipradilol preserved peak developed pressure during reperfusion. CONCLUSIONS: Despite its properties as a beta-adrenergic blocking agent, nipradilol was able to precondition the heart, probably as a result of its ability to produce nitric oxide.

Action Potentials↗
PubMed1996

Phorbol-12,13-dibutyrate and pinacidil cardioplegia. Novel forms of myoprotection.

BACKGROUND: Activation of either protein kinase C or the ATP-sensitive potassium channel has been shown to induce the preconditioning response. METHODS AND RESULTS: To investigate whether preconditioning activation adjuvant to hypothermic blood cardioplegia enhances postischemic contractile recovery, 23 adult (0.5 to 1.0 year old) sheep were randomized to receive cardioplegia based on the hyperpolarizing ATP-sensitive potassium channel opener pinacidil, the protein kinase C activator 4 beta-phorbol-12, 13-dibutyrate (PDBu), or standard potassium-magnesium (K1/Mg2+). All groups underwent 60 minutes of 10 degrees C antegrade intermittent blood cardioplegia and 30 minutes of reperfusion. Mechanics were assessed on modified right heart bypass by the preload recruitable stroke work relation and the end-systolic pressure-volume relation. Diastolic function was modeled by the exponential time constant of isovolumic left ventricular pressure decay (Tau) and the "stiffness" coefficient (beta) of the end-diastolic pressure volume relation. Recovery rhythm was defined by the first electrical activity seen during reperfusion. Cardioplegic arrest and preconditioning induced by pinacidil provided superior recovery of contractile function compared with PDBu (100% versus 57% recovery, P < .05) or K+/Mg+ (100% versus 56% recovery, P < .05). Active (Tau) and passive (beta) diastolic function was preserved by all three arrest modalities. Hearts treated with pinacidil demonstrated a rapid recovery of a coordinated contraction pattern, which was offset by a reperfusion tachycardia, whereas PDBu arrest was associated with ventricular fibrillation on reperfusion. CONCLUSIONS: Preconditioning during cardioplegic arrest is agent specific, feasible at cold temperatures, and may be superior to the use of standard K+/Mg2+ cardioplegia.

Animals↗
PubMed1996

A brief period of retrograde hyperthermic perfusion enhances myocardial protection from global ischemia: association with accumulation of Hsp 70 mRNA and protein.

The induction of heat shock proteins in the myocardium has been suggested as a possible intervention to allow for enhanced cardioprotection. We examined the cardioprotective effects of Hsp 70 induction in a clinically relevant model, in which a brief period of retrograde hyperthermic perfusion (42 degrees C) was applied for 15 min, only 5 min prior to global ischemia and reperfusion in the isolated perfused rat heart. Our results indicate that in retrograde hyperthermic perfused hearts (n = 17) there was enhanced dP/dT, end diastolic pressure, and peak developed pressure during normothermic reperfusion following 15 min of global ischemia when compared to control hearts perfused at 37 degrees C (n = 18). Northern analysis indicated Hsp 70 mRNA, in retrograde hyperthermic perfused hearts, was increased 9.0 +/- 0./70-fold (P < 0.001) by 30 min and 9.1 +/- 0.45-fold (P < 0.001) by 60 min of normothermic reperfusion. Western analysis revealed that the Hsp, heat inducible 72 kD protein was increased 1.74 +/- 0.35-fold (P < 0.001) by 30 min and 1.79 +/- 0.31-fold at 60 min of normothermic reperfusion when compared to no ischemia hearts. Our results demonstrate that the use of 15 min of retrograde hyperthermic perfusion, only 5 min prior to global ischemia and reperfusion, provide for enhanced myocardial functional recovery. Enhanced myocardial functional recovery was associated with the accumulation of Hsp 70 mRNA and the Hsp 72 kD protein.

Animals↗
PubMed1996

Physiological and cellular mechanisms of myocardial protection.

BACKGROUND: Despite 40 years of clinically successful open heart surgery, cardiac surgeons continue to seek the ideal myoprotective strategy to minimize perioperative myocardial damage and maximize clinical outcome. Although crude measures, such as length of hospital stay or operative mortality rate, may provide useful administrative data, the ultimate outcome measure of significance to the patient is the lack of operatively induced myocellular injury. METHODS: An ideal biological marker would thus quantitate the number of viable and functioning myocytes remaining postoperatively. The purpose of the present review was to develop the theoretical framework for modern approaches to intraoperative myocardial protection when considering the fundamental principles of physiological and cellular ischemic mechanisms. RESULTS AND CONCLUSIONS: It is hoped that this review provides insight into the implementation of these fundamental concepts developed at the University of Illinois and applied in our present experiences in advanced myocardial muscle mechanics and molecular biology.

Animals↗
PubMed1996

Developmental differences in cytosolic calcium accumulation associated with surgically induced global ischemia: optimization of cardioplegic protection and mechanism of action.

OBJECTIVE: The effect of cardioplegic solutions with high concentrations of potassium or magnesium (or both) on cytosolic calcium accumulation was investigated with fura-2 in isolated perfused mature (n = 24) and aged (n = 24) rabbit hearts. METHODS: We compared cytosolic calcium accumulation before ischemia (control), during 30 minutes of ischemia and 30 minutes of reperfusion under global ischemia, or after treatment with potassium (20 mmol/L), magnesium (20 mmol/L), or both. RESULTS: Cytosolic calcium accumulation was increased during global ischemia in the mature heart (from 178.7 +/- 24.2 in the control group to 393.6 +/- 25.5 nmol/L; p < 0.005) and in the aged heart (from 187.4 +/- 18.7 in the control group to 501.0 +/- 46.1 nmol/L; p < 0.005). Potassium reduced cytosolic calcium accumulation during ischemia in both the mature and aged hearts (300.9 +/- 23.2 and 365.2 +/- 27.7 nmol/L, respectively; p < 0.05 vs global ischemia). Magnesium and potassium/magnesium completely controlled cytosolic calcium accumulation in the mature heart (198.7 +/- 27.5 nmol/L; p < 0.01 vs global ischemia and p < 0.05 vs potassium: 182.3 +/- 22.7 nmol/L; p < 0.05 vs global ischemia and potassium, respectively). Magnesium and potassium/magnesium attenuated cytosolic calcium accumulation in the aged heart (261.3 +/- 26.7, 262.3 +/- 25.2 nmol/L, respectively; p < 0.01 vs global ischemia). These changes in cytosolic calcium accumulation correlated with improved post-ischemic ventricular function. To investigate the mechanism(s) of magnesium-supplemented cardioplegic inhibition of cytosolic calcium accumulation, we performed parallel studies (n = 43) using nifedipine, ryanodine, and dimethylthiourea. Nifedipine with or without ryanodine reduced cytosolic calcium accumulation. Dimethylthiourea did not alter cytosolic calcium accumulation during global ischemia. Our results suggest that cytosolic calcium accumulation during global ischemia was mainly increased via the sarcolemmal 1-type calcium channel and the sarcoplasmic reticulum calcium-release channel. The modulating action of potassium/magnesium cardioplegia on cytosolic calcium accumulation during ischemia would appear to act through the inhibition of the myocardial 1-type calcium channel and the sarcoplasmic reticulum calcium-release channel. CONCLUSION: Senescent cardiac dysfunction correlates with increased ischemia-induced cytosolic calcium accumulation. Magnesium-supplemented potassium cardioplegia ameliorates this age-related phenomenon at normothermia and may have important implications in myocardial protection in the elderly population.

Aging↗
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

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↗