Jiankang Sun

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.

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.

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.

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.

An interleaved T1-T2* imaging sequence for assessing myocardial injury.

We developed a sequence by which T1- and T2*-weighted images can be acquired simultaneously and demonstrated its validity for assessing myocardial injury. The interleaved T1-T2* imaging sequence consisted of one preparatory pulse (a 90 degrees pulse) and a gradient-echo imaging sequence with a dynamically variable echo time varying between 4.2 msec for T1-weighted imaging and 15 msec for T2*-weighted imaging. The sequence was tested and validated on isolated blood-perfused pig hearts (n = 4). We found that contrast agent-induced T1 and T2* effects were clearly delineated during the first-pass and steady-state periods of a contrast agent (gadolinium diethylenetriaminopentaacetic acid). With a bolus injection of contrast agent, the maximum changes in T2* signal intensity occur significantly earlier than the changes in T1 signal. We also found that the maximum change in T1 signal intensity during the first pass of contrast agent was significantly greater in a reperfused-infarcted region than in normal regions. The suppression of T2* signal was similar in both regions. At steady state of contrast agent, T2* signal intensities gradually recovered to a significantly higher level in the reperfused-infarcted region than in normal regions. This suggests that the contrast agent diffused into the intracellular space, indicating the loss of cell membrane integrity. As a result, T1 signal intensity was also higher in the reperfused-infarcted myocardium than in normal myocardium. T1- and T2*-weighted images can be acquired simultaneously. The interleaved T1-T2* sequence is useful in assessing myocardial injury.

Dynamic manganese-enhanced magnetic resonance imaging can detect chronic cryoinjury-induced infarction in pig hearts in vivo.

The purpose was to investigate whether MnCl(2) can serve as an MRI contrast agent to detect chronic cryoinjury infarction in pigs in vivo and whether MnCl(2) causes significant hemodynamic disturbances. Hearts were subjected to a topical 2 min cryothermia to establish myocardial infarction (MI). Thereafter GdDTPA-enhanced MRI was performed at 0, 1, 2 and 3 weeks using a 3 T scanner. Four weeks post-cryoinjury the pigs underwent in vivo Mn-enhanced magnetic resonance imaging (MEMRI). MnCl(2) (70 μmol/kg, 14 min) was infused i.v. intermittently (n = 4) or continuously (n = 5) and T(1)-weighted images were acquired every 2 min simultaneously recording heart rate and arterial blood pressure. Either infusion scheme led to an immediate increment in MR signal intensity (SI) within the left ventricular (LV) blood pool and LV normal and cryoinjured myocardium, which reached a maximum at the end of infusion. No significant difference was observed between the normal and cryoinjured myocardium. After infusion termination, SI decreased faster within the LV blood pool and the MI, as compared with the normal myocardium in either group, resulting in significant contrast between the MI and normal tissue (intermittent: 18 ± 7 vs 49 ± 13%, p = 0.002; continuous: 19 ± 8 vs 36 ± 9%, p = 0.004). Infarction sizes were similar in Mn(2+)- and GdDTPA-enhanced images at 4 and 3 weeks post injury, respectively. Thus, in vivo MEMRI differentiated infarcted from normal myocardium in pig hearts subjected to 4-week cryoinjury. Compared with intermittent infusion, continuous infusion minimized hemodynamic fluctuations.