Search PubMed⌕ Search

Biomedical subjects

R Deslauriers

Publications and source records attributed to R Deslauriers.

At least 55 records · Page 3Linked to original sources
PubMed1997

Spectral analysis of intercycle heart fluctuations in the diethyl-ether-anaesthetized or pithed rat treated with l-hyoscyamine.

1. Within the context of neural regulation of the activity of sinus node pacemaker cells, the study of heart rate variability, as explored in the frequency domain by spectral analysis, was proposed about 15 years ago as a quantitative tool for the evaluation of short-term autonomic cardiovascular control. It has since been postulated that the two main oscillations observed, one at low and the other at high frequency, may respectively be markers of sympathetic vs. vagal efferent cardiac activity, and that the low- and high-frequency signals may reflect a reciprocal or 'push-pull' relationship between sympathetic and parasympathetic control. 2. In our power spectra assessment, ECG R-R intervals were submitted to fast Fourier transformation analysis in order to study the mechanisms underlying the control of heart beats in rats. Data were acquired in conditions of steady arterial blood pressure and cardiac and respiratory activity (spontaneous or artificially stimulated) in diethyl-ether-anaesthetized and pithed rats, as well as in a group of control rats, all in the presence and absence of l-hyoscyamine. 3. With increasing doses of the parasympathetic antagonist, the fractal dimension of the time-series structure remained stable in most cases. The low-frequency spectral component narrowed with increasing drug doses and the high-frequency band underwent either no, or only very slight, changes. 4. In these rodent assays, the low- and high-frequency signals cannot be interpreted as a push-pull relationship between sympathetic and parasympathetic control.

Anesthetics, Inhalation↗
PubMed1997

Evaluation of hydroxyethyl-starch-ferrioxamine as an intravascular MR contrast agent for assessment of myocardial perfusion.

PURPOSE: The present study was carried out to evaluate a new intravascular contrast agent hydroxyethyl-starch-ferrioxamine (HES-FO) for assessment of myocardial perfusion. MATERIAL AND METHODS: Isolated pig hearts were perfused with a crystalloid cardioplegic solution in a Langendorff apparatus. MR images were acquired along the short cardiac axis using T1- and T2*-weighted methods. Gd-DTPA and HES-FO were used as the standard extracellular and test contrast agents, respectively. RESULTS: We found that T1-weighted signal intensity was not significantly affected by HES-FO, but increased significantly in presence of Gd-DTPA. On the other hand, HES-FO resulted in a rapid, transient but significant decrease in T2*-weighted signal intensity. Although Gd-DTPA also decreased T2*-weighted signal intensity considerably, it took much longer for the T2*-weighted signal intensity to return to its initial steady-state with Gd-DTPA than with HES-FO. Moreover, increasing the dose of HES-FO (from 0.0023-0.0138 mmol/kg b.w.) had no effect on the time at which the T2* effect reached its maximum or on the duration of the T2* effect. However, these times and durations were affected significantly by increasing the dose of Gd-DTPA (0.0023-0.027 mmol/kg b.w.). CONCLUSION: The results suggest that HES-FO provides information regarding myocardial vascular flow which cannot be obtained using Gd-DTPA. It is expected that the combined use of intravascular and extracellular type contrast agents will allow more complete assessment of tissue perfusion.

Animals↗
PubMed1997

A new technique of coronary artery ligation: experimental myocardial infarction in rats in vivo with reduced mortality.

In vivo models of myocardial infarction following coronary artery ligation in the rat still suffer from high early mortality and a low rate of success of myocardial infarction. This study investigated the possibility of reducing early mortality and increasing the rate of myocardial infarction by modifications of surgical techniques. Eighteen rats were divided into two groups: normal control (3 rats) and ligation (15 rats). The major modifications of surgical techniques used in this study include: (1) no exteriorization of the heart, (2) ligation of the origins of the branches rather than the main trunk of the left coronary artery, (3) removal of air from the chest after closure, (4) supplying oxygen immediately after extubation. Following surgery, the rats recovered uneventfully and 11 rats were alive after 16 weeks. One rat, with a large myocardial infarction, died 2 h after surgery. Early mortality (during surgery and 1 week after surgery) was 6.7% with a success rate of myocardial infarction of 85%. The left ventricle in the ligation group showed significant dilation relative to normal and sham-operated control hearts (317% of control hearts, p < 0.001). However, myocardial mass did not increase. The average infarct size was 33%. These results demonstrate that a reduction in early mortality and an increased success rate of myocardial infarction can be achieved by modifications of surgical techniques.

Analysis of Variance↗
PubMed1997

Na(+)-H+ exchange inhibition at reperfusion is cardioprotective during myocardial ischemia-reperfusion; 31P NMR studies.

To help resolve the controversy as to whether or not Na(+)-H+ exchange is functioning during reperfusion of the ischemic myocardium we assessed the effects of dimethylamiloride (DMA, an amiloride analogue possessing selectivity for inhibition of the Na(+)-H+ exchanger) on cardiac function and intracellular pH during ischemia-reperfusion. Studies were performed in the presence of bicarbonate (modified Krebs-Henseleit buffer) or in the nominal absence of bicarbonate (HEPES buffer) in order to determine if similar cardioprotection and effects on intracellular pH were observed in the presence and absence of bicarbonate dependent transport processes. Isovolumic rat hearts were perfused in the Langendorff mode at a constant pressure of 80 mm Hg and subjected to 28 min total global ischemia at 37 degrees C. Intracellular pH was determined from the pH dependent shift of the inorganic phosphate peak in 31P nuclear magnetic resonance spectra. DMA (20 microM) was infused for either 2.5 min before ischemia, for the initial 5 min of reperfusion, or at both time intervals. DMA had no effect on the intracellular pH during ischemia. Intracellular pH returned to pre-ischemic levels within 2.5 min of reperfusion in bicarbonate buffer. This normalization of pH was slower in HEPES perfusate. In both bicarbonate and HEPES perfused hearts all drug dosing regimens caused a significant increase in the recovery of mechanical function after reperfusion and slowed the recovery of intracellular pH during reperfusion. These results suggest that the Na(+)-H+ exchanger is activated during reperfusion of the ischemic myocardium, that this activation of the exchanger contributes to ischemia-reperfusion induced cardiac dysfunction and that administration of an inhibitor of Na(+)-H+ exchange at reperfusion significantly attenuates the deleterious effects of exchanger activation.

Amiloride↗
PubMed1996

Evaluation of cardiac 31P magnetic resonance spectroscopy: reviewing NMR principles.

31P magnetic resonance spectroscopy (MRS) has been used for several decades as an analytical tool in cardiac research and is quickly emerging as a diagnostic tool, due to its ability to continuously and noninvasively monitor levels of high energy phosphates, inorganic phosphate, and intracellular pH in localized regions of the myocardium. This article provides a brief review of basic MRS principles, presents some current techniques of localized spectroscopy related to experimental and clinical cardiac research, and discusses their advantages and disadvantages.

Animals↗
PubMed1996

Neuronal damage after hypothermic circulatory arrest and retrograde cerebral perfusion in the pig.

BACKGROUND: Antegrade and retrograde cerebral perfusion during hypothermic circulatory arrest (HCA) has been reported to provide better brain protection during operation than hypothermic circulatory arrest alone. However, the efficacy of these techniques remains to be fully determined, especially when used for prolonged periods. We used a pig model to evaluate the histopathologic consequences of HCA and the potential benefit of cerebral perfusion during HCA. METHODS: Twenty-two pigs were divided into four groups and exposed to either anesthesia alone, 120 minutes of HCA (15 degrees C), 120 minutes of retrograde cerebral perfusion at 15 degrees C during HCA, or 120 minutes of antegrade cerebral perfusion at 15 degrees C during HCA, and then reperfused for 60 minutes under cardiopulmonary bypass at 37 degrees C. The brains were perfusion fixed at the end of the experiments and examined by light microscopy. RESULTS: There were no morphologic changes in any areas of the brains in the anesthesia group, and very minor changes in some areas of the brains in the antegrade cerebral perfusion. group. Varying severity of neuronal damage was found in the brains of all the pigs in the HCA and retrograde cerebral perfusion groups. The severity of ischemic damage in the brain showed the following descending order: hippocampus (CA4), caudate nucleus, cerebral cortex, putamen, thalamus, Purkinje cells of the cerebellum, pons, and mesencephalic gray matter. In the hippocampus the order of damage was CA4, CA3, polymorphous layer of the dentate gyrus, prosubiculum, CA2, CA1, and granule cell layer of the dentate gyrus. The damage in the retrograde cerebral perfusion group was less severe relative to the HCA group in many areas (no significance except mesencephalic gray matter). CONCLUSIONS: These results demonstrate that the pattern of neuronal damage in pigs subjected to HCA and retrograde cerebral perfusion differs from the traditional pattern in that the caudate nucleus and hippocampal CA4 region are the most vulnerable to ischemia-hypoxia. Our results also suggest that antegrade cerebral perfusion prevented ischemic damage to the brain and retrograde cerebral perfusion provided some protection but moderately severe damage occurred.

Animals↗
PubMed1996

Cerebral protection during moderate hypothermic circulatory arrest: histopathology and magnetic resonance spectroscopy of brain energetics and intracellular pH in pigs.

OBJECTIVE: We evaluated the effect of antegrade and retrograde brain perfusion during moderate hypothermic circulatory arrest at 28 degrees C. METHODS: Phosphorus 31-magnetic resonance spectroscopy was used to follow brain energy metabolites and intracellular pH in pigs during 2 hours of ischemia and 1 hour of reperfusion. Histopathologic analysis of brain tissue fixed at the end of the experimental protocol was performed. Fourteen pigs were divided into two experimental groups subjected to antegrade (n = 6) or retrograde (n = 8) brain perfusion. Anesthesia (n = 8) and hypothermic cardiopulmonary bypass groups (15 degrees C, n = 8) served as control subjects. In the antegrade and retrograde brain perfusion groups, the initial bypass flow rate was 60 to 100 ml x kg(-1) x min(-1). In the antegrade group, the brain was perfused through the carotid arteries at a flow rate of 180 to 210 ml x min(-1) during circulatory arrest at 28 degrees C. In the retrograde group, the brain was perfused through the superior vena cava at a flow rate of 300 to 500 ml x min(-1) during circulatory arrest at 28 degrees C. RESULTS: The intracellular pH was 7.1 +/- 0.1 and 7.2 +/- 0.1 in the anesthesia and hypothermic bypass groups, respectively. Brain intracellular pH and high-energy metabolites (adenosine triphosphate, phosphocreatine) did not change during the course of the 3.5-hour study. In the antegrade group, adenosine triphosphate and intracellular pH were unchanged throughout the protocol. In the retrograde perfusion group, the intracellular pH level decreased to 6.4 +/- 0.1, and adenosine triphosphate and phosphocreatine levels decreased within the first 30 minutes of circulatory arrest and remained at low levels until the end of reperfusion. High-energy phosphates did not return to their initial levels during reperfusion. Histopathologic analysis of nine regions of the brain showed good preservation of cell structure in the anesthesia, hypothermic bypass, and antegrade perfusion groups. The retrograde perfusion group showed changes in all the regions examined. CONCLUSIONS: The study shows that moderate hypothermic circulatory arrest at 28 degrees C with antegrade brain perfusion during circulatory arrest protects the brain but that retrograde cerebral perfusion at 28 degrees C does not protect the brain.

Adenosine Triphosphate↗
PubMed1996

Magnetic resonance studies of the effects of cardiovascular surgery on brain metabolism and function.

Neurologic and neuropsychologic impairment are important sequelae of cardiac surgery in general and of coronary artery bypass graft surgery in particular. Although estimates of incidence vary, the numbers affected are considerable. Despite the ubiquity of such effects and the general consensus that impairments originate from ischemic injury secondary to microemboli produced during surgery, the nature of the underlying brain injuries remains poorly understood. Precise, and preferably quantitative, definition of the localization and nature of the underlying injuries is a precondition for the rigorous evaluation of the efficacy of prophylactic measures. The ability of magnetic resonance imaging (MRI) to detect surgically related lesions and the course of brain swelling is described, as are potential improvements in imaging sensitivity. Results of an experimental program studying chemical sequelae of surgery in a pig model are presented. MR spectroscopy can provide noninvasive information on the biochemical changes in brain and brain metabolism that permit empirical evaluation of various neuroprotective interventions. Functional MRI provides a means of studying the neuropsychologic mechanisms most often affected by cardiac surgery. Experimental data are presented that demonstrate that two such mechanisms, selective attention and working memory, can be imaged successfully. Perfusion mapping, combined with functional imaging, allows for the quantitative study of flow and functional activation. Applied to structures such as the cingulate, these techniques permit comparison of surgical sequelae with processes such as normal aging. MRI technology offers the possibility of improved anatomic, chemical, and functional definition of the effects of cardiac surgery on the brain.

Animals↗
PubMed1996

Cytoplasmic phosphates in Na(+)-K+ balance in KCN-poisoned rat heart: a 87Rb-, 23Na-, and 31P-NMR study.

The effect on intracellular Na+ ([Na+]i) and Rb+ fluxes if reduced [ATP]/ [ADP] and increased Pi has been investigated by 1 mM potassium cyanide (KCN) or KCl (control) infusion (24 min) in Langendorff perfused rat hearts. 87Rb, 23Na, or 31P nuclear magnetic resonance (NMR) spectra were acquired to measure intracellular Rb+ (a congener for K+, 20% substitution), Na+, and phosphates. KCN infusion (14-24 min) caused decreases in phosphocreatine (34 +/- 12% of initial), ATP (64 +/- 17), and Rb content (71 +/- 7) and increases in Pi (273 +/- 65) and [Na+]i (210 +/- 52). Dimethylamiloride (10 microM) did not change the rate of Na+ accumulation. The rate constant of unidirectional Rb+ efflux (min-1) increased during KCN treatment by 70% (0.061 +/- 0.006 vs. 0.036 +/- 0.004, P = 0.0001). KCN-stimulated Rb+ efflux was inhibited by glibenclamide (Glib, 10 microM. 0.042 +/- 0.009, P = 0.0001 vs. KCN) and alpha-cyano-4-hydroxycinnamate (0.5 mM, 0.047 +/- 0.008, P < 0.002 vs. KCN). KCN moderately decreased the Rb+ influx rate (to 82 +/- 17%, P = 0.01), which was depressed more significantly in the presence of Glib (47 +/- 17%, P = 0.03). We suggest that inhibition of Na(+)-K(+)-adenosinetriphosphatase (ATPase) by Pi is responsible for intracellular Na+ accumulation, whereas K+ loss is associated with both activation of ATP-sensitive K+ channels and the K(+)-lactate-cotransporter and inhibition of Na(+)-K(+)-ATPase.

Animals↗
PubMed1995

Antegrade and retrograde continuous warm blood cardioplegia: a 31P magnetic resonance study.

BACKGROUND: Retrograde normothermic blood cardioplegia has been shown to provide myocardial protection during certain bypass procedures. However, a number of animal studies have shown less than optimal myocardial protection with this technique. METHODS: Isolated, beating porcine hearts were perfused antegradely (aortic root pressure = 75 to 95 mm Hg) for 30 minutes. Arrest was induced and maintained for 60 minutes with high K+ blood cardioplegia delivered either antegradely (n = 8) or retrogradely (n = 8) (coronary sinus pressure = 35 to 55 mm Hg). Perfusate was switched to normokalemic blood for recovery of sinus rhythm (30 minutes). Intracellular pH, creatine phosphate, inorganic phosphate, and adenosine triphosphate were monitored continuously and noninvasively with phosphorus 31 magnetic resonance spectroscopy throughout the experiment, and functional variables (rate-pressure product and the positive and negative first derivatives of left ventricular pressure) were assessed concurrently. RESULTS: Antegrade cardioplegia maintained high-energy metabolites, intracellular pH, and myocardial function. Retrograde normothermic blood cardioplegia resulted in an increase in inorganic phosphate (197% +/- 15% of control) and a decrease in creatine phosphate (51% +/- 6% of control). There was no significant difference in myocardial function between the two groups (p > 0.05). The magnetic resonance spectroscopy data indicate ischemia occurred within 2 minutes of the initiation of retrograde perfusion. CONCLUSIONS: This study suggests that retrograde normothermic blood cardioplegia causes a transition of the myocardium to ischemic metabolism in the normal porcine heart.

Adenosine Triphosphate↗
PubMed1995

Contractile dysfunction caused by normothermic ischaemia and KCL arrest in the isolated pig heart: a 31P NMR study.

The aims of this study were to assess (1) whether contractile dysfunction caused by ischaemia under hyperkalaemic conditions ("cardioplegic ischaemia") is associated with impaired energy production or abnormalities in regulation of contractility and (2) whether hyperkalaemia itself contributes to contractile dysfunction. We used 31P and 23Na NMR spectroscopy in conjunction with measurements of mechanical function and oxygen consumption in Langendorff perfused pig hearts to evaluate the mechanism of contractile failure caused by (1) total global cardioplegic (17 mM [K+]) ischaemia (36 degrees C, 50 min KCl arrest, 45 min ischaemia, 20 min reflow with high KCl) and (2) KCl arrest alone (115 min) without flow cessation. KCl arrest plus ischaemia and subsequent reperfusion (Group I) resulted in decreases in ATP (mean +/- S.D.; 61 +/- 13% of initial, n = 5; P < 0.01) and pressure-rate product (PRP) (31 +/- 9%, n = 17; P = 0.0001) while phosphocreatine (PCr), Pi, total creatine (Cr) and intracellular Na+ levels were unaffected. KCl arrest itself (Group II, n = 6) did not affect PCr, ATP or total Cr levels but decreased the PRP to 59 +/- 12% (P < 0.001). Oxygen consumption rates (Vo2) were reduced in both groups to similar levels (67 +/- 18, P < 0.01 and 77 +/- 13%, P < 0.02, respectively). The efficiency of energy conversion to mechanical work (PRP/delta VO2) decreased to 51 +/- 15 (P < 0.001) and 67 +/- 13% (P < 0.012) of initial levels, respectively. To assess metabolic and contractile reserves of post-ischaemic (n = 7) and KCl-treated (n = 3) hearts, the effects of isoproterenol (Iso) and increased Ca2+ were compared with those in normal beating hearts (Group III, n = 3). In all groups treatment with Iso (0.1 micron) greatly increased PRP (to 526 +/- 116, 203 +/- 16 and 198 +/- 8% of the level prior to stimulation (baseline), P < 0.01, respectively) and Vo2 (162 +/- 9, 153 +/-16 and 128 +/-10% of baseline, P < 0.05, Respectively). Increasing [Ca2+] from 1 to 1.66 mM produced less stimulation than Iso: PRP increased to 195 +/- 23, 156 +/- 13 and 163 +/- 22% (P < 0.05) and Vo2 increased to 138 +/- 22 (P < 0.05), 115 +/- 4 and 120 +/- 10% of baseline in Groups I, II and III, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Diphosphate↗
PubMed1995

Protective effect of amiloride during hypothermic hyperkalemic preservation: a 31P NMR study in isolated pig hearts.

To assess the possible role of Na+/H+ exchange in ischemia-reflow damage during cold preservation, pig hearts retrogradely perfused with Krebs-Henseleit (KH) bicarbonate buffer were arrested by increasing [K+] (to 17 mM), cooled (10 degrees C) and subjected to no flow ischemia for 15 h in the absence (C, n = 5) and in the presence of 0.5 mM amiloride (A, n = 5). A was added 7 min prior to ischemia and removed after 3 min reflow. 31P nuclear magnetic resonance (NMR) spectra were continuously acquired and functional indices were assessed prior to and after ischemia. Before reflow, the levels of phosphocreatine (PCr), ATP, inorganic phosphate (Pi)+phosphomonoesters (PME) and cytosolic pH in C and A did not differ: C, 12 +/- 7, 56 +/- 13, 427 +/- 75% of initial and 5.90 +/- 0.20; A, 15 +/- 4, 82 +/- 21, 371 +/- 60% and 5.90 +/- 0.19, respectively; no contracture occurred. Upon reflow with hyperkalemic buffer PCr recovery in A-treated hearts was greater than in C (73 +/- 21 v 49 +/- 13%, P < 0.05) and parallel increases in left ventricular end diastolic (LVEDP) and perfusion pressure took place in both groups, however these parameters remained lower in A-treated hearts. Upon switching to KH buffer the oxygen uptake rate (VO2) was higher in A than in C (79 +/- 18 v 59 +/- 6%, P < 0.05) whereas the differences in the pressure-rate product (PRP, 51 +/- 21 in A v 38 +/- 11% in C) and LVEDP (16 +/- 11 in A v 24 +/- 7 mmHg in C) did not reach statistically significant levels. Adjusting LVEDP in both groups to the same levels (19 +/- 6 v 21 +/- 9 mmHg in C) by changing balloon volume resulted in significant difference in PRP (61 +/- 19% v 42 +/- 6% in C, P < 0.02). The coronary resistance measured in beating hearts remained lower in A than in C (34.5 +/- 3.0 v 57 +/- 11 mmHg/(ml/min g), P = 0.04). To estimate contractile and metabolic reserves post-ischemic heart were challenged by increasing [Ca2+] in the perfusate from 1.0 to 1.6 mM. PRP and VO2 increased; PRP reached 71 +/- 32 (A) and 54 +/- 10% (C) and VO2 remained higher in A: 90 +/- 16 (A) v 62 +/- 4% (C) (P = 0.01) of preischemic levels. We suggest that Na+/H+ exchange may contribute to ischemia-reflow damage during cold preservation of isolated pig hearts.

Adenosine Diphosphate↗
PubMed1995

A 31p-magnetic resonance study of antegrade and retrograde cerebral perfusion during aortic arch surgery in pigs.

To evaluate the effect of hypothermic circulatory arrest on brain metabolism, we used 31P-magnetic resonance spectroscopy to monitor brain metabolites in pigs during 2 hours of ischemia and 1 hour of reperfusion. Twenty-eight pigs were divided into five groups. Anesthesia (n = 5) and hypothermic cardiopulmonary bypass groups (n = 5) served as controls. In the circulatory arrest (n = 6), antegrade perfusion (n = 6), and retrograde (n = 6) brain perfusion groups, the bypass flow rate was 60 to 100 ml.kg-1.min-1. In the antegrade group, the brain was perfused via the carotid arteries at a blood flow rate of 180 to 200 ml.min-1 during circulatory arrest at 15 degrees C. In the retrograde group, the brain was perfused through the superior vena cava at a flow rate of 300 to 500 ml.min-1 during circulatory arrest at 15 degrees C. The intracellular pH was 7.1 +/- 0.1 and 7.3 +/- 0.1 in the anesthesia and hypothermic cardiopulmonary bypass groups, respectively. In the circulatory arrest group, the intracellular pH decreased to 6.2 +/- 0.1 and did not recover to its initial value (7.0 +/- 0.1) during reperfusion (p < 0.05 compared with the value obtained from the control groups at the corresponding time). Inorganic phosphate did not return to its initial level during reperfusion. In three animals in this group, levels of high-energy phosphates, adenosine triphosphate and phosphocreatine, recovered partially but did not reach the levels observed before arrest. In the group receiving antegrade perfusion, cerebral metabolites and intracellular pH were unchanged throughout the protocol. During circulatory arrest in the retrograde perfusion group the intracellular pH decreased to 6.4 +/- 0.1 and recovered fully during reperfusion (7.1 +/- 0.1). High-energy phosphates also returned to their initial levels during reperfusion. These studies show that deep hypothermic circulatory arrest with antegrade brain perfusion provides the best brain protection of the options investigated.

Adenosine Triphosphate↗
PubMed1995

A 31P-nuclear magnetic resonance study of intermittent warm blood cardioplegia.

This study was designed to assess the effects of intermittent warm blood cardioplegia on myocardial energy metabolites, intracellular pH, and contractile function. The isolated blood-perfused pig hearts were divided into three groups. After 30 minutes of control perfusion, the hearts in group 1 (n = 10) received 90 minutes of continuous warm (37 degrees C) blood cardioplegia; the hearts in group 2 (n = 9) received six 5-minute periods of warm blood cardioplegia, interrupted by six 10-minute episodes of ischemia (37 degrees C). The hearts were then reperfused for 30 minutes. The hearts in group 3 underwent 150 minutes of control perfusion without cardioplegia or ischemic episodes. Phosphorus 31-nuclear magnetic resonance spectra showed that a 10-minute interruption of warm blood cardioplegia decreased phosphocreatine levels and intracellular pH by approximately 47% (p < 0.01) and 0.12 unit (p < 0.05), respectively, and increased inorganic phosphate levels by approximately 87%, whereas resumption of cardioplegia for 5 minutes resulted in almost 100% recovery of phosphocreatine and inorganic phosphate levels and intracellular pH. More important, subsequent interruptions did not result in any cumulative changes in phosphocreatine level, inorganic phosphate level, or intracellular pH beyond those changes observed after the initial cardioplegic interruption. Moreover, during reperfusion there were no significant differences in adenosine triphosphate and phosphocreatine levels among the three groups of hearts. Furthermore, hearts from groups 1 and 2 showed comparable recovery of contractile function. These results indicate that six 10-minute interruptions and six 5-minute restorations of warm blood cardioplegia caused only mild and reversible changes in myocardial energy metabolites and intracellular pH and these changes were not cumulative. This study suggests that antegrade intermittent warm blood cardioplegia may provide as much myocardial protection as does antegrade continuous warm blood cardioplegia in the normal heart.

Adenosine Triphosphate↗
PubMed1995

Intermittent antegrade warm cardioplegia reduces oxidative stress and improves metabolism of the ischemic-reperfused human myocardium.

The aim of this study was to compare the effect of intermittent antegrade warm blood cardioplegia and intermittent antegrade cold blood cardioplegia on myocardial metabolism and free radical generation of the ischemic-reperfused human myocardium. Thirty patients undergoing mitral valve procedures were randomly allocated to two groups: group 1 (15 patients) received warm blood cardioplegia and group 2 (15 patients), cold blood cardioplegia. Myocardial metabolism was assessed before aortic clamping, 1 minute after crossclamp removal, and after 20 minutes of reperfusion, by collecting blood simultaneously from the radial artery and coronary sinus. All samples were analyzed for lactate, creatine kinase, reduced and oxidized glutathione, ascorbic acid, fluorescent products of lipid peroxidation, and leukocyte activation (elastase). In all patients, early reperfusion was associated with significant coronary sinus lactate release. In group 2, but not in group 1, significant coronary sinus release of reduced and oxidized glutathione, fluorescent products of lipid peroxidation, and creatine kinase was also found; moreover, arterial-coronary sinus difference of ascorbic acid content was increased only in group 2, suggesting a transmyocardial consumption of this antioxidant vitamin. After 20 minutes of reperfusion, coronary sinus lactate release was no longer present in group 1, whereas significant production was still evident in group 2. In this group, significant coronary sinus release of fluorescent products of lipoperoxidation and reduced and oxidized glutathione was also observed at this time. No significant release of elastase from the coronary sinus was noted in the two groups throughout the study. The left ventricular stroke work index measured at the end of the study indicated a better functional recovery in group 1 than in group 2. In conclusion, intermittent antegrade warm blood cardioplegia protects the myocardium from ischemia-reperfusion injury better than intermittent antegrade cold blood cardioplegia; this phenomenon may be partly due to the decreased tissue oxidant burden mediated by intermittent warm blood cardioplegia.

Aged↗
PubMed1995

Pathways of Rb+ influx and their relation to intracellular [Na+] in the perfused rat heart. A 87Rb and 23Na NMR study.

The aims of this study were to characterize the routes of influx of the K+ congener, Rb+, into cardiac cells in the perfused rat heart and to evaluate their links to the intracellular Na+ concentration ([Na+]i) using 87Rb and 23Na nuclear magnetic resonance (NMR) spectroscopy. The rate constant for Rb+ equilibration in the extracellular space was 8.5 times higher than that for the intracellular space. The sensitivity of the rate of Rb+ accumulation in the intracellular space of the perfused rat heart to the inhibitors of the K+ and Na+ transport systems has been analyzed. The Rb+ influx rates were measured in both beating and arrested hearts: both procaine (5 mmol/L) and lidocaine (1 mmol/L) halved the Rb+ influx rate. In procaine-arrested hearts, the Na+,K(+)-ATPase inhibitor ouabain (0.6 mmol/L) decreased Rb+ influx by 76 +/- 24% relative to that observed in untreated but arrested hearts. Rb+ uptake was insensitive to the K+ channel blocker 4-aminopyridine (1 mmol/L). The inhibitor of Na+/K+/2 Cl- cotransport bumetanide (30 mumol/L) decreased Rb+ uptake only slightly (by 9 +/- 8%). Rb+ uptake was dependent on [Na+]i: it increased by 58 +/- 34% when [Na+]i was increased with the Na+ ionophore monensin (1 mumol/L) and decreased by 48 +/- 9% when [Na+]i was decreased by the Na+ channel blockers procaine and lidocaine. Dimethylamiloride (15 to 20 mumol/L), an inhibitor of the Na+/H+ exchanger, slightly reduced [Na+]i and Rb+ entry into the cardiomyocytes (by 15 +/- 5%). 31P NMR spectroscopy was used to monitor the energetic state and intracellular pH (pHi) in a parallel series of hearts. Treatment of the hearts with lidocaine, 4-aminopyridine, dimethylamiloride, or bumetanide for 15 to 20 minutes at the same concentrations as used for the Rb+ and Na+ experiments did not markedly affect the levels of the phosphate metabolites or pHi. These data show that under normal physiological conditions, Rb+ influx occurs mainly through Na+,K(+)-ATPase; the contribution of the Na+/K+/2 Cl- cotransporter and K+ channels to Rb+ influx is small. The correlation between Rb+ influx and [Na+bdi during infusion of drugs that affect [Na+]i indicates that, in rat hearts at 37 degrees C, Rb+ influx can serve as a measure of Na+ influx. We estimate that, at normothermia, at least 50% of the Na+ entry into beating cardiac cells is provided by the Na+ channels, with only minor contributions (< 15%) from the Na+/K+/2 Cl- cotransporter and the Na+/H+ exchanger.

Animals↗
PubMed1995

The role of magnesium in myocardial preservation.

The purpose of this review is to look at the role of magnesium in the formation of preservation and reperfusion solutions for the ischaemic heart. Preservation of the heart during cardiac surgery procedures, including cardiac transplantation, can be divided into distinct phases: arrest, cold storage in the case of transplantation, global ischaemia during implantation or cardiac surgery procedures, followed by reperfusion when the heart is rewarmed and restarted. Although the magnesium ion can play a significant role in myocardial protection, it is important to recognize the different types of protection required during these different phases of surgical procedures. The rationale for the inclusion of magnesium in cardioplegic solutions is threefold: (i) for its negative inotropic effect; (ii) to prevent ischaemia-induced magnesium loss; (iii) to influence cellular ionic movements. Preservation temperature as well as the concentration of other ionic constituents present in the preservation solution alter the effects of magnesium. Results obtained from animal models suggest that elevated magnesium (16 mM) is beneficial to the hypothermic preservation of hearts with extracellular type solutions, especially when calcium is elevated in the solution formulation. Research has shown that the amplitude of the inotropic effect of magnesium varies from one species to another so that the beneficial effect of magnesium is inferior in the less sensitive species. Using the human atrial trabecular preparation as a model for myocardial preservation, we have assessed the effects of elevated magnesium on the recovery of developed force, both for long-term preservation (24 h) during hypothermic arrest (4 degrees C) and for reperfusion during rewarming of the trabeculae. No clear pattern emerged when the ratio of calcium to magnesium was altered in St Thomas' I and II solutions used for the storage. However, when the atrial trabecular preparation was rewarmed in a Krebs Henseleit buffer containing an elevated level of magnesium (16 mM), a greater number of trabeculae reached a greater developed force and had higher levels of energetic metabolites than when the magnesium in the Krebs Henseleit buffer was 1.2 mM. Several studies have suggested that an elevated magnesium prevents calcium overload by competing with this ion at the membrane, and reduces the workload, while ATP reserves and ion homoeostasis are re-established. The role of the magnesium ion in hypothermic preservation of the human myocardium is still not clear after many clinical and experimental studies and requires further investigation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗