Biomedical subjects

R Deslauriers

Publications and source records attributed to R Deslauriers.

At least 37 records · Page 2Linked to original sources

PubMed1998

Temperature dependence of monovalent cation fluxes in isolated rat hearts: a magnetic resonance study.

Ion flux studies were performed on Langendorff-perfused rat hearts using 87Rb, 7Li and 23Na NMR at 36, 20 and 10 degreesC, and at constant extracellular pH (7.40). Using 31P NMR, the intracellular pH was estimated and the high energy phosphate content monitored. Compared to 36 degreesC (k=0.044+/-0.015 min-1), our measurements showed incomplete Rb+ efflux with a dramatically (5-fold) increased rate constant, k, at 20 degreesC, k=0.238+/-0.080 min-1. 5 microM glibenclamide, a KATP-channel inhibitor, completely depressed the hypothermia-activated Rb+ efflux at this temperature (k=0.052+/-0. 018 min-1). 7Li NMR efflux studies on KCl-arrested hearts at 20 degreesC also showed an increase (3-fold) in efflux rate constant: k=0.090+/-0.003 min-1 relative to its value at 36 degreesC. At 10 degreesC, both Rb+ and Li+ showed efflux rate constants similar to those observed at 36 degreesC, k=0.071+/-0.016 min-1 and k=0.050+/-0. 005 min-1, respectively, and the washout was complete. 31P NMR at 36, 20 and 10 degreesC indicated cytosolic alkalinization at pH values of 7.05, 7.21 and 7.40, respectively. The ion transport data could be interpreted in terms of a myocyte model allowing for temperature-dependent changes in transport coefficients. The incomplete efflux of Rb+ at 20 degreesC may indicate the existence of a mitochondrial Rb+-pool with a very low Rb+ permeability for efflux. These findings correlate with previously observed membrane phase transitions in these systems.

Animals↗

PubMed1998

Retrograde cerebral perfusion results in flow distribution abnormalities and neuronal damage. A magnetic resonance imaging and histopathological study in pigs.

BACKGROUND: In the past few years, although significant efforts have been made to assess flow distribution during retrograde cerebral perfusion with microspheres, dye, or hydrogen clearance, flow distribution in real time is still undefined. We used MR perfusion imaging to monitor flow distribution in the brain during and after deep hypothermic circulatory arrest (DHCA) with antegrade or retrograde cerebral perfusion (ACP or RCP). METHODS AND RESULTS: Thirteen pigs were divided into 2 groups and exposed to 120 minutes of either RCP (n = 7) or ACP (n = 6) at 15 degrees C, followed by 60 minutes of cardiopulmonary bypass (CPB) at 37 degrees C. During DHCA, the brain was perfused antegradely through the common carotid artery or retrogradely through the superior vena cava at pressures of 60 to 70 mm Hg and 20 to 25 mm Hg in the ACP and RCP groups, respectively. Esophageal temperature was monitored continuously. MR perfusion images were acquired every 30 minutes before, during, and after DHCA. The brain was perfusion-fixed with formaldehyde solution for histopathology at the completion of each experiment. During initial normothermic CPB, MR perfusion imaging showed a nearly uniform distribution of flow in the brain. The same pattern was maintained with a significant increase in regional cerebral blood volume during ACP and reperfusion in the ACP group. RCP provided little or no detectable blood distribution to the brain, resulting in poor reperfusion of many areas of the brain on reflow with CPB at 37 degrees C. The total area suffering poor reperfusion was significantly higher in the RCP group than the ACP group. Histopathology showed no morphological changes in any area of the brain in the ACP group, whereas varying severity of neuronal damage was observed in different regions of the brain in the RCP group. CONCLUSIONS: ACP preserves uniform blood distribution and normal morphology of brain tissue after prolonged DHCA. RCP provides very little blood to the tissue of the brain. A 120-minute period of RCP results in abnormal flow distribution and neuronal damage during reperfusion. The damage resulting from shorter periods of RCP remains to be assessed.

Animals↗

PubMed1998

Kinetics of ATP-sensitive K+ channels in isolated rat hearts assessed by 87Rb NMR spectroscopy.

An experimental model was developed to evaluate the effects of activators and inhibitors of K(ATP) channels on unidirectional K+ fluxes in the whole heart. Isolated rat hearts perfused in the Langendorff mode were equilibrated with Pi-free Krebs-Henseleit buffer (KH buffer) containing 0.94-2.14 mM RbCl and 3.76 mM KCl (20-36% of K+ substituted by Rb+). Rb+ efflux was initiated by removing Rb+ from the perfusate and 87Rb spectra were acquired continuously with a 1-2 min time resolution. In hearts with normal energetics, the efflux of Rb+ fit a monoexponential function, and the rate constant did not depend on intracellular [Rb+]. Agents depressing excitability and heart rate (HR), such as 0.6 mM lidocaine (Lido), 10 microM carbachol (carb) and 20 mM MgSO4, inhibited Rb+ efflux such that the rate constant, k (10(3)/min), decreased from 50+/-1.2 in the beating heart to 26+/-1, 40+/-1.1 and 19+/-1.2, respectively. In contrast, high [K+] (21 mM) did not affect the k value (50+/-4.5), independently of the presence or absence of bumetanide (Bum, 30 microM) and glibenclamide (Glib, 5 microM). Dinitrophenol (DNP, 0.2 mM) added in the presence of high [K+] + Bum increased k three-fold, to 160+/-5. This effect was associated with a significant decrease in phosphocreatine (PCr, <10% of initial) and ATP ( 15%) levels, and a 7-fold increase in the Pi level, assessed by 31P-NMR spectroscopy. Glib completely reversed the effect of DNP. Pinacidil (Pin, 20-80 microM) did not affect the k value either in beating control hearts or in the presence of Carb or KCl + Bum. Moreover, under conditions of moderate metabolic stress induced by 0.05 mM DNP (PCr, 35%; ATP, 65%), where half-maximal activation of K(ATP) channels occurred, Pin did not further activate Rb+ efflux. We conclude that:(1) heart rate-independent Rb+ efflux accounts for 40-80% of the total Rb+ efflux in beating (300 bpm) rat hearts;(2) DNP-activated Rb+ efflux is a good model for testing inhibitors of KATP channels in whole hearts; and (3) Pin is not an effective K(ATP) channel opener in the rat heart model.

2,4-Dinitrophenol↗

PubMed1998

Three-dimensional 87Rb imaging of isolated pig hearts: effects of regional ischemia.

The aim of this work was to investigate whether 1) Rb uptake is reduced in ischemic myocardium, and 2) 87Rb three-dimensional (3D) imaging can detect the ischemic area. Hearts of domestic pigs (n = 8, 20-30 kg) were perfused retrogradely with Krebs-Henseleit buffer in a 7-T, 40-cm horizontal bore magnet interfaced with Bruker MSLX spectrometer. Control (C) and ischemic (I) (45 min ligation of the left anterior descending coronary artery (LAD)) hearts were loaded with Rb+ by perfusion with a Rb(+)-containing solution (2-4.7 mM, 30-100% of K+ substitution) for 35 min and 87Rb (C) or 31P (ischemic area in I) spectra were acquired. After mechanical arrest with 0.6-0.9 mM lidocaine, 87Rb images (7 min each, 1 cm3 resolution) were acquired (30-40 min) in the presence of Rb(+)-containing perfusate. Subsequently, the hearts were stained with Evans blue (EB) and samples taken for measurements of Rb+ content. In the Group C, distribution of Rb+ in the left ventricle and the intensities of the 3D 87Rb images were uniform. In the ischemic area (Group I), verified by the lack of EB staining and changes in 31P spectra, the images showed a reduced intensity, which corresponded to decreased Rb+ content (33 +/- 11% of the normal). Thus, 87Rb imaging reveals damaged cells detecting reduced Rb+ content in the ischemic area.

Animals↗

PubMed1998

Observation of two inorganic phosphate NMR resonances in the perfused hypothermic rat heart.

The effect of hypothermia on isolated perfused rat hearts was studied with 31P NMR. Hearts were continuously perfused with phosphate-free Krebs-Henseleit buffer while the perfusate temperature was adjusted. Perfusate pH was kept at 7.40 +/- 0.02 throughout the experiments. Using the chemical shift difference between PCr and Pi the intracellular pH was estimated. At 36, 20, and 10 degreesC a cytosolic alkalinization at a pH of 7.05 +/- 0.04, 7.21 +/- 0.05, and 7.40 +/- 0.03 was observed, respectively. At 10 degreesC two Pi resonances were observed with a separation of 0.25 ppm. This resonance corresponded to a Pi resonance of a cellular compartment with a local pH of 7.78 +/- 0.06, likely mitochondrial. This additional resonance disappeared upon warming of the hearts back to 36 degreesC.

Animals↗

PubMed1998

Does simultaneous antegrade/retrograde cardioplegia improve myocardial perfusion in the areas at risk? A magnetic resonance perfusion imaging study in isolated pig hearts.

OBJECTIVE: This study was designed to determine whether simultaneous antegrade/retrograde cardioplegia improves myocardial perfusion in areas supplied by occluded vessels. METHODS: Isolated pig hearts placed in a Langendorff preparation were divided into two groups. The left anterior descending coronary artery was occluded at its origin. In group 1 (n = 7), simultaneous antegrade/retrograde cardioplegia was conducted with use of a single perfusion unit with tubing in a Y-shaped configuration at the end, joined to the aorta and the coronary sinus. In group 2 (n = 8) simultaneous antegrade/retrograde cardioplegia was performed with two separate units, one for antegrade delivery of cardioplegic solution and the other for retrograde cardioplegic solution delivery. Myocardial perfusion in the region supplied by the left anterior descending artery and the region not supplied by this artery was assessed by magnetic resonance imaging, with use of a magnetic resonance contrast agent. The contrast agent was introduced into the common perfusion line in group 1 and into the aortic line only in group 2. RESULTS: Magnetic resonance images showed that the myocardium in the region supported by the left anterior descending artery could not be perfused with antegrade cardioplegic solution because of occlusion of the artery. During simultaneous antegrade/retrograde cardioplegia, however, the myocardium in the left anterior descending region was perfused by approximately 40% to 50% (group 1) or 20% to 30% (group 2) of the degree of perfusion in the region not perfused by the left anterior descending artery (100%). Almost no cardioplegic solution was delivered to the heart through the coronary sinus route during simultaneous antegrade/retrograde cardioplegia in both groups of hearts. Myocardial perfusion in the region supported by the left anterior descending artery was heterogeneous during simultaneous antegrade/retrograde cardioplegia. CONCLUSIONS: Simultaneous antegrade/retrograde cardioplegia significantly improved myocardial perfusion in jeopardized areas of the myocardium. The jeopardized myocardium was mainly perfused by the solution drained from the adjacent normal tissue. Elevated pressure at the coronary sinus during simultaneous antegrade/retrograde cardioplegia is responsible for the redistribution of antegradely delivered cardioplegic solution.

Animals↗

PubMed1998

Spectral analysis of intercycle heart fluctuations in the diethyl-ether-anaesthetized or pithed rat treated with prazosin, dl-propranolol, endothelin-1, alpha-r atriopeptin and ACE-inhibitors.

1. Frequency-domain spectral analysis of stationary ECG R-R intervals was made by fast Fourier transformation (FFT) in conditions of monitored arterial blood pressure and respiratory activity in diethyl-ether-anaesthetized and pithed adult rats. This technique yields a number of parameters which allow quantitative evaluation of the non-random distribution of the mean values obtained in time-domain studies. The frequency-analysis method enables the overall heart rate variability to be broken down into its various constituents, which are differently affected by physiological loading and capable of selective reactivity to pharmacological agents. 2. The low-frequency spectral component obtained by breaking down the total spectral density power, i.e. the appropriate variability signal (band width < 0.15 Hz) and a higher-frequency band corresponding to spontaneous (0.80-1.60 Hz) or artificially imposed (0.75 Hz) respiratory activity were estimated and their integrated areas evaluated as absolute powers or normalized fractional values. 3. The power of the high-frequency spectral component increased in all animal preparations under treatment with prazosin, dl-propranolol, endothelin-1 and the angiotensin converting enzyme (ACE) inhibitors captopril, lisinopril, quinapril and ramipril. The power of the low-frequency band increased under alpha-r atriopeptin and ACE inhibitors in the pithed preparations only, and decreased in the anaesthetized animals. 4. The new power spectrum features and trends detected indicate that these time-independent, model-dependent cardiovascular and respiratory markers are subject to some form of complex peptidergic control. 5. The relative roles of the various factors operating in the genesis of these short-term changes in spectral power in the low- and high-frequency bands cannot be interpreted as indicating a reciprocal push-pull relationship between sympathetic and parasympathetic control. 6. The study findings, however, can be interpreted as providing evidence of a different and to some extent alternative form of integrative cardiovascular control persisting in the pithed rats (i.e. in the 'peripheral', CNS-destroyed preparations). 7. New areas of theoretical and applied research are being developed in the (auto)classification of (iso)receptors and drug analogues through exploration of multiple physiological and pharmacokinetic parameters in the frequency-domain. Furthermore, model-independent frequency-domain methods not requiring stationary data will afford scope for even more significant developments by separating the overlapping dynamic processes from a whole series of correlated effects.

Animals↗

PubMed1998

Cardiac magnetic resonance spectroscopy.

The article reviews cardiac magnetic resonance spectroscopy (MRS) in Canada. 31P MRS has been used to study cardiac energetics and intracellular pH in hearts subjected to ischemia-reperfusion and to evaluate the effects of pharmacological interventions. 23Na, 87Rb, and 7Li MRS have provided unique probes to study ion balance and fluxes in intact tissue under normal and stressful physiological conditions. 1H MRS has been used to monitor the accumulation of lactate and lipids in hearts subjected to ischemia-reperfusion and follow the effects of diet on cardiac lipid levels and function. The isolated rat heart has been used most commonly to study the effects of pharmacological agents on energy balance, pH, ion fluxes, and contractile function of the heart subjected to ischemia-reperfusion. The pig heart has been developed as an alternative to the rodent heart because its metabolism is more similar to that of the human heart. Human atrial appendages have been useful in evaluating the effects of preservation strategies (temperature, composition of preservation solutions) on energy levels. The pig heart model has been useful in evaluating the effects of preservation solutions on cardiac function of hearts destined for transplantation. An isolated blood-perfused pig heart model has been developed to assess the effects of cardioplegic strategies on the preservation of contractile function of hearts following surgery on the heart. An in vivo canine model has been used to study myocardial infarction and the effects of therapies to reduce the infarct zones and areas of the heart at risk of infarction. Studies of human hearts in vivo have provided insight into the metabolic adaptations that occur in individuals living at high altitudes.

Adenosine Triphosphate↗

PubMed1997

Does retrograde warm blood cardioplegia provide equal protection to both ventricles? A magnetic resonance spectroscopy study in pigs.

BACKGROUND: The degree of protection provided to the right ventricle during retrograde continuous normothermic blood cardioplegia (RCNBC) remains controversial. The purpose of this study was to determine whether RCNBC is able to provide "adequate" nutritive flow to both ventricles to prevent ischemic metabolism in normal swine hearts. Localized 31P magnetic resonance spectroscopy (MRS) was used to monitor the changes in energy metabolism and intracellular pH (pHi) in each ventricle separately. METHODS AND RESULTS: Isolated normal swine hearts received 20 minutes of antegrade continuous normothermic blood cardioplegia (ACNBC) for collection of control (baseline) data, followed by 20 minutes of RCNBC. This protocol was repeated four times in five hearts and twice in two hearts. Perfusion pressure was maintained between 70 to 85 and 38 to 43 mm Hg during ACNBC and RCNBC, respectively. pHi, creatine phosphate (PCr), inorganic phosphate (Pi), and ATP were measured continuously in each ventricle during ACNBC and RCNBC, using localized 31P MRS with two surface coils. RCNBC resulted in a significant increase in Pi (LV 222% and RV 244% of the baseline levels, respectively) and a decrease in PCr (left ventricle [LV] to 68% and right ventricle [RV] to 31% of the baseline levels, respectively) in both ventricles relative to ACNBC. The PCr level was significantly lower in the RV than in the LV (31% versus 68%, P<.001) during RCNBC. In one series of experiments (n=5) where ACNBC and RCNBC were alternated every 20 minutes (ACNBC, RCNBC, ACNBC, RCNBC, ACNBC) for a total of 100 minutes, Pi and PCr recovered completely. A continuous and significant decrease in ATP was observed in the RV, and no recovery of ATP was found when switching from RCNBC to ACNBC. No significant decrease in ATP was observed in the LV. pHi remained unchanged in both ventricles during alternate ACNBC and RCNBC. CONCLUSIONS: Energy metabolism in the RV is less well preserved than in the LV during RCNBC. A combination of ACNBC and RCNBC seems to provide good cardiac protection as measured by the recovery of cardiac energetics and pHi.

Adenosine Triphosphate↗

PubMed1997

The effect of circulatory arrest and retrograde cerebral perfusion on microtubule-associated protein 2: an immunohistochemical study in pig hippocampus.

Microtubule-associated protein 2 (MAP2) immunohistochemical labeling in the hippocampus was studied to assess the protective effect of brain perfusion during surgery requiring hypothermic circulatory arrest in 24 pigs exposed to anesthesia alone (control), 120 min of complete circulatory arrest at 15 degrees C, min of retrograde cerebral perfusion at 15 degrees C, or 120 min of anterograde cerebral perfusion at 15 degrees C. Pigs were reperfused for 60 min and sacrificed. In the control anterograde perfusion groups, the intensity of MAP2 labeling was similar in all regions of the hippocampus. Circulatory arrest and retrograde perfusion resulted in significant reduction of MAP2 labeling (28% and 38% respectively of control, P < 0.001) of neurons in the CA1 region. MAP2 labeling may be useful for assessing early damage in the hippocampus in this model.

Animals↗

PubMed1997

Lithium ion as a probe of Na+ channel activity in isolated rat hearts: a multinuclear NMR study.

The aim of this study was to analyze Na+ fluxes in whole perfused hearts using Li+ as a Na+ congener and 7Li-nuclear magnetic resonance as a detection method. Hearts were equilibrated for 32 min with 15 mM LiCl added to P1-free Krebs-Henseleit buffer (intracellular space (ICS) [Li+] = 21.5 +/- 3.4 mM). Li+ efflux was monitored using a Li(+)-free perfusate. The effects of drugs on Li+ efflux were studied by adding the compounds 4 min prior to initiating Li+ washout. 7Li-NMR spectra were collected every 2 min at 139.95 MHz. Li+ efflux was biphasic with rate constants (k +/- SD, min-1) of 0.5 +/- 0.1 (extracellular) and 0.09 +/- 0.01 (ICS). Li+ efflux from ICS was dependent on heart rate (HR): cardiac arrest produced by 1 mM lidocaine or 20 mM KCl reduced k to 1/3 of its control value (Lidocaine, 0.030 +/- 0.004; KCl, 0.035 +/- 0.003). Increasing concentrations of carbachol (0.2-3.0 microM) caused a gradual decrease in HR and revealed a linear relationship between k and HR. In KCl-arrested hearts the Na+ channel opener veratridine increased k by 60% (10 microM, 0.057 +/- 0.006). Dimethylamiloride did not affect k (10 microM, 0.024 +/- 0.006) in Lidocaine-arrested hearts. Bumetanide (30 microM, 0.094 +/- 0.013), nifedepine (0.33 microM, 0.088 +/- 0.009), Bay K8644 (0.1 microM, 0.080 +/- 0.002), 4-aminopyridine (1.5 mM, 0.076 +/- 0.006) and cromakalim (10 microM, 0.088 +/- 0.006) did not significantly affect either k or HR. Li+ efflux from myocytes in perfused rat heart is mediated mainly by voltage-dependent Na+ channels.

Animals↗

PubMed1997

Effects of cromakalim and glibenclamide on myocardial high energy phosphates and intracellular pH during ischemia-reperfusion: 31P NMR studies.

ATP sensitive potassium channel (KATP) openers (e.g. cromakalim) are thought to be cardioprotective during ischemia-reperfusion, while KATP blockers (e.g. glibenclamide) may potentiate ischemia-reperfusion damage. We studied cardiac energetics and intracellular pH, by 31P magnetic resonance spectroscopy, during ischemia-reperfusion of buffer perfused, isolated rat hearts in the presence of cromakalim (10 microM) or glibenclamide (1, 10 and 50 microM). Hearts were subjected to 25 min total global ischemia at 36.5 degrees C and reperfused for 45 min. Pre-treatment with cromakalim delayed the time to ischemic contracture (19.3 +/- 1.5 min v 15.3 +/- 0.6 for control, P < 0.05) and significantly improved recovery of function at 45 min reperfusion (84 +/- 11% pre-ischemic rate pressure product (RPP) v 38 +/- 5 for control, P < 0.05). This was accompanied by an attenuation in the loss of ATP during ischemia. Pre-treatment with glibenclamide decreased the time to ischemic contracture: 16.1 +/- 0.8 min. 15.1 +/- 0.7, 12.0 +/- 1.2 (P < 0.01) and 9.5 +/- 0.9 (P < 0.001) for control, 1, 10 and 50 microM glibenclamide respectively. 50 microM glibenclamide significantly improved functional recovery at 45 min reperfusion but 1 and 10 microM were without effect; 24 +/- 6, 22 +/- 4, 29 +/- 4 and 58 +/- 7% (P < 0.05) of pre-ischemic RPP for control, 1, 10 and 50 microM glibenclamide. During ischemia, intracellular ATP was depleted more rapidly in the presence of 50 microM glibenclamide and intracellular acidosis was significantly attenuated (final pH 6.3 v 5.8 for control). 50 microM glibenclamide also decreased tissue lactate content at the end of ischemia (75 +/- 3 mumol/g dry weight v 125 +/- 18 for control, P < 0.05) and this attenuation of lactate accumulation and consequent decreased intracellular acidosis may be responsible for the cardioprotection observed under these conditions. These latter effects are unlikely to be related to glibenclamide's KATP blocking activity. This study demonstrates that blocking of myocardial KATP does not potentiate ischemia-reperfusion injury and, in addition, illustrates the important role played by intracellular acidosis in myocardial ischemia-reperfusion injury.

Adenosine Triphosphate↗

PubMed1997

Oxygen regulation of energy metabolism in isolated pig hearts: a near-IR spectroscopy study.

UNLABELLED: Intracellular pO2 in cardiac muscle is determined by the balance between its diffusion from vascular (VS) to intracellular space (IS) and uptake by mitochondria. Cessation of mechanical work decreases O2 demand and should reduce the O2 gradient between VS and IS. In this work, the effects of arterial pO2 (pO2a) on myoglobin (Mb) oxygenation, O2 uptake and lactate formation rates [V(O2) and V(Lac), micromol/min/g wet weight, respectively] in beating and KCl-arrested pig hearts were compared. pO2a was decreased stepwise (five steps, 10 min/step) from 528+/-24 to 54+/-19 mmHg by changing the ratio of O2/CO2 (95:5%) to N2/CO2 (95:5%) in the gas mixture from 100/0 through 50/50, 25/75, 10/90 to 0/100. While recording mechanical function, visible/near-infrared (near-IR) spectra (400-2500 nm) were acquired from the left ventricular wall every 45 s (32 scans) using a fiber-optic light guide connected to an NIRSystems spectrometer. Relative MbO2 in the epicardium + midmural layer and the epicardium was estimated from absorbance changes (second derivative) at 764 and 584 nm, respectively. In beating hearts, a decrease in pO2a resulted in a decrease in MbO2 (similar in both layers) and V(O2) (from 1.26+/-0.15 to 0.22+/-0.10) and an increase in V(Lac) from 0 to 2.43+/-0.76. In arrested hearts an increase in V(Lac) (0.55+/-0.24) was observed only at the lowest pO2a and the Mb oxygenation curve was shifted towards lower vascular pO2 [(pO2a+pO2v)/2] by ;160 mmHg. Oxygen consumption (oxygen flux) correlated linearly with calculated values of the oxygen gradients between the vascular and cytoplasmic spaces in both beating and arrested hearts. However, the diffusion rate constant was 3.5 times lower in arrested hearts. CONCLUSIONS: (1) hypoxia in KCl-arrested hearts results in only moderate activation of anaerobic glycolysis; (2) oxygenation of the epicardial and midmural LV layers is similar; and (3) a large pO2 gradient exists between VS and IS in beating and arrested crystalloid-perfused hearts.

Adenosine Triphosphate↗

PubMed1997

Beyond hyperkalemia: beta-blocker-induced cardiac arrest for normothermic cardiac operations.

BACKGROUND: Four experimental protocols were carried out to assess the ability of esmolol to induce and maintain reversible cardiac arrest under continuous normothermic (37 degrees C) perfusion. METHODS AND RESULTS: In the first protocol, 8 perfused rat hearts were subjected to 20, 60, 90, and 120 minutes of esmolol arrest, after which positive and negative first derivative of pressure, heart rate, left ventricular developed pressure, and left ventricular end-diastolic pressure were evaluated. Arrest was achieved 45 to 60 seconds after beginning the infusion of esmolol. Mechanical arrest was achieved before electrical arrest. In the second protocol, dose-response curves were obtained using isolated (Langendorff) rat and rabbit (n = 6) hearts. The concentrations of esmolol varied from 0.084 to 6.7 mmol/L and from 0.12 to 1.45 mmol/L in the rat and rabbit heart experiments, respectively. In the third protocol, the effects of 20 minutes of normothermic (37 degrees C) ischemia on the function of isolated rat hearts perfused with esmolol-containing Krebs solution were compared with those using high-potassium (25 mmol/L) Krebs solution. Group A subjects (n = 9) received the ischemic injury after being perfused (and arrested) for 20 minutes with either esmolol or potassium (KCl, 25 mmol/L). Group B subjects (n = 10) received the same ischemic insult before being perfused with either esmolol or potassium. Esmolol-treated hearts showed better recovery than those receiving potassium, in terms of +/- dP/dt (p < 0.01), left ventricular systolic pressure (p < 0.01), and left ventricular developed pressure (p < 0.009). Finally, the fourth protocol was done to evaluate the effects of esmolol in a clinically relevant experimental model. Pigs were divided into esmolol (n = 6) and potassium (n = 5) groups and subjected to normothermic cardiopulmonary bypass and a 1-hour period of cardiac arrest. Twenty minutes after stopping infusion of the cardioplegic agents, all animals were weaned off bypass. There were no statistically significant differences between the groups. CONCLUSIONS: Esmolol hydrochloride can be used as effectively as potassium for inducing and maintaining predictable and reversible cardiac arrest during normothermic cardiac operations.

Adrenergic beta-Antagonists↗

PubMed1997

Retrograde cerebral perfusion provides limited distribution of blood to the brain: a study in pigs.

OBJECTIVE: The objective of this study was to investigate flow distribution during retrograde and antegrade cerebral perfusion with India ink as a marker. METHODS: Ten pigs received cerebral perfusion with a solution containing 50% filtered India ink for 5 minutes either antegradely through both internal carotid arteries at a flow of 180 to 200 ml/min (n = 5) or retrogradely via the superior vena cava at a flow of 300 to 500 ml/min (n = 5). The brains were then fixed for quantitative measurement of the density of ink-filled capillaries (reported as a percentage of the total selected area). The assessment was done with the use of an in-house software program. RESULTS: In the antegrade cerebral perfusion group, the intracranial arterial and venous systems were completely filled with ink. The gray matter was colored uniformly black, and light coloring was observed in the white matter. During retrograde cerebral perfusion, the majority of ink was returned to the inferior vena cava, and only a small amount of ink was found in the innominate artery draining from the brain. Massive ink filling was observed in the sagittal sinus and other venous sinuses in all the pigs. Vessels on the surface of the brain and large vessels in the brain were also well filled with ink. However, only 10% of capillaries were filled with ink during retrograde cerebral perfusion relative to the number observed with antegrade cerebral perfusion. CONCLUSIONS: Retrograde cerebral perfusion supplies a limited amount of blood to brain tissue, which flows mainly through superficial and large deep cerebral vessels.

Animals↗

PubMed1997

Assessment of retrograde cardioplegia with magnetic resonance imaging and localized 31P spectroscopy in isolated pig hearts.

OBJECTIVE: This study was done to determine whether retrograde delivery of cardioplegic solution provides uniform blood flow to the myocardium supplied by an occluded coronary artery and whether it maintains myocardial energy levels beyond the coronary occlusion. METHODS: Isolated pig hearts were used. A hydraulic occluder was placed at the origin of the left anterior descending coronary artery. The perfusion pressure for retrograde delivery of cardioplegic solution was controlled at 40 to 50 mm Hg. Magnetic resonance imaging and localized 31P magnetic resonance spectroscopy were used to assess myocardial perfusion and energy metabolism, respectively. RESULTS: Magnetic resonance perfusion images (n = 7) showed that the perfusion defect that occurred during antegrade delivery of cardioplegic solution (as a result of the occlusion of the left anterior descending coronary artery) resolved during retrograde delivery of cardioplegic solution. Retrograde perfusion delivered similar amounts of flow to the jeopardized myocardium as it did to other areas of the myocardium. However, the distribution of cardioplegic solution by the retrograde route was heterogeneous (cloudlike) across both ventricular walls. 31P magnetic resonance spectra showed that the ischemic changes induced by occlusion of the left anterior descending artery during antegrade perfusion were greatly alleviated by retrograde perfusion; however, it took longer for retrograde cardioplegia (n = 7, 17.08 minutes) to restore the levels of inorganic phosphate/phosphocreatine relative to the effect of releasing the left anterior descending artery occluder during antegrade delivery of cardioplegic solution (n = 7, 5.3 minutes). CONCLUSIONS: First, retrograde delivery of cardioplegic solution provides sufficient flow to the myocardium beyond a coronary occlusion to maintain near normal levels of energy metabolites, and second, the efficacy of the retrograde route of cardioplegic solution delivery (in terms of distribution of the solution and rate of myocardial energy recovery) is significantly lower than that of the antegrade route.

Animals↗

PubMed1997

Aspartate/glutamate-enriched blood does not improve myocardial energy metabolism during ischemia-reperfusion: a 31P magnetic resonance spectroscopic study in isolated pig hearts.

OBJECTIVE: Our objective was to test the effects of exogenous L-aspartate and L-glutamate on myocardial energy metabolism during ischemia-reperfusion. METHODS: Phosphorus 31-magnetic resonance spectroscopy was used to observe cellular energetics and intracellular pH in isolated pig hearts perfused with blood (group A, n = 8) or blood enriched with 13 mmol/L each of L-aspartate and L-glutamate (group B, n = 6). The hearts were subjected to 30 minutes of total normothermic ischemia and then reperfused for 40 minutes. Two hearts from each group were inotropically stimulated by titration with calcium after normokalemic reperfusion. Left ventricular function was measured with the use of a compliant balloon and oxygen consumption was calculated. RESULTS: Magnetic resonance spectroscopy showed no decrease in the rate of energy decline during ischemia for group B versus group A. No significant differences were observed between the two groups in terms of myocardial function, oxygen consumption, or the rate or extent of high-energy phosphate recovery after normokalemic reperfusion or inotropic stimulation. Inotropic stimulation of postischemic hearts, however, led to dramatic improvement in myocardial function in both groups (p < 0.05 for all parameters) and significant improvement in oxygen consumption (p = 0.01). CONCLUSIONS: In a normal, isolated, blood-perfused pig heart subjected to 30 minutes of total normothermic ischemia, (1) enrichment of the perfusate with aspartate/glutamate before and after ischemia affects neither myocardial energy metabolism during ischemia-reperfusion nor postischemic recovery of myocardial function or oxygen consumption and (2) inotropic stimulation can recruit significant postischemic function and sufficient aerobic respiration to support it, irrespective of aspartate/glutamate enrichment.

Adenosine Triphosphate↗

PubMed1997

Spectral analysis of intercycle heart fluctuations in Xenopus laevis, conscious or spinalized, treated with calcium channel blockers. Part I.

1. In this study, electrocardiographic second lead tracings were recorded and analyzed online and offline in the conscious and spinalized Xenopus laevis under control conditions and after treatment with at least two effective doses of racemic diltiazem, nifedipine and racemic verapamil hydrochlorides. 2. Heart rates (HR) and intercycle heart rate power spectra (IHRPS) were calculated in the various experimental conditions. 3. Dose-dependent bradycardia was found in most cases, which was associated with dose-related increases in the overall dynamic range of the largest peak of HR variability (increased IHRPS), this being particularly marked at the higher nifedipine dose. The frequency position of the largest peak was unchanged in the spinalized preparation, as well as in the various treatments. 4. These findings may contribute toward a more complete pharmacodynamic definition of calcium channel blockers in their current therapeutic use.

Animals↗