A modified protocol for retrograde cerebral perfusion: magnetic resonance spectroscopy in pigs.

OBJECTIVES: Retrograde cerebral perfusion (RCP) has been employed to protect the brain during cardiovascular surgery, requiring temporary hypothermic circulatory arrest (HCA). However, the protocol used for RCP remains to be modified if prolonged HCA is expected. The aim of this study was to determine the efficacy of a modified protocol for this purpose. METHODS: After establishment of HCA at 15°C, 14 pigs were subjected to 90-min RCP using either the conventional protocol (i.e. alpha-stat strategy, 25-mmHg perfusion pressure and occluded inferior vena cava, Group I, n = 7) or the new protocol (i.e. pH-stat strategy, 40-mmHg perfusion pressure and unoccluded inferior vena cava, Group II, n = 7). After being rewarmed to 37°C, pigs were perfused for another 60 min. Phosphorus-31 magnetic resonance spectroscopy was used to track the changes of brain high-energy phosphates [i.e. adenosine triphosphate and phosphocreatine (PCr)] and intracellular pH (pHi). At the end, brain water content was measured. RESULTS: During RCP, high-energy phosphates decreased in both groups, whereas adenosine triphosphate decreased much faster in Group I (10.4 ± 4.3 vs 30.4 ± 4.4% of the baseline, P = 0.007, 60-min RCP). After rewarming, the recovery of high-energy phosphates and pHi was much slower in Group I (PCr: 55.7 ± 9.1 vs 78.4 ± 5.1% of the baseline, P = 0.046; adenosine triphosphate: 26.6 ± 10.6 vs 64.8 ± 4.6% of the baseline, P = 0.007; pHi: 6.5 ± 0.4 vs 7.1 ± 0.1, P = 0.021 at 30-min normothermic perfusion after rewarming). Brain tissue water content was significantly higher in Group I (81.1 ± 0.4 vs 79.5 ± 0.4%, P = 0.016). CONCLUSIONS: Application of the modified RCP protocol significantly improved cerebral energy conservation during HCA and accelerated energy recovery after rewarming.

Can stunned hearts be resuscitated? Evaluation of aspartate/glutamate secondary blood cardioplegia using magnetic resonance spectroscopy.

Objectives: Reperfusion of ischemic hearts with warm, substrate-enriched, blood cardioplegia may alleviate post-ischemic metabolic and functional derangements. This study investigates this possibility using (31)P magnetic resonance (MR) spectroscopy. Methods: Fifteen blood-perfused Langendorff pig hearts were subjected to 30 min of total, normothermic ischemia. Control hearts (n=8) were reperfused with blood for 40 min. Experimental hearts (n=7) received 20 min of aspartate/glutamate (asp/glu) enriched blood cardioplegic solution, followed by 20 min of normal blood. (31)P MR spectroscopy was used to observe cellular energetics and intracellular pH (pHi) throughout the experiments. Left-ventricular function and myocardial oxygen consumption were evaluated before and after ischemia. Results: MR spectra showed no improvement in the rate or extent of high-energy phosphate recovery with asp/glu cardioplegia, but showed a transient increase in pHi during cardioplegic reperfusion (p<0.05). This, however, did not affect post-ischemic recovery of high energy metabolites, myocardial function or oxygen consumption. Conclusions: This study raises questions regarding the potential beneficial effects of asp/glu enriched secondary cardioplegic solution on functional or metabolic status of stunned pig hearts. Extrapolation of these results to humans should be viewed with caution. Keywords: Magnetic resonance; Pig heart; Aspartate; Glutamate; Cardioplegia; Myocardial stunning.

Adipose-derived stem cells are an effective cell candidate for treatment of heart failure: an MR imaging study of rat hearts.

This study assessed the potential therapeutic efficacy of adipose-derived stem cells (ASCs) on infarcted hearts. Myocardial infarction was induced in rat hearts by occlusion of the left anterior descending artery (LAD). One week after LAD occlusion, the rats were divided into three groups and subjected to transplantation of ASCs or transplantation of cell culture medium (CCM) or remained untreated. During a 1-mo recovery period, magnetic resonance imaging showed that the ASC-treated hearts had a significantly greater left ventricular (LV) ejection fraction and LV wall thickening than did the CCM-treated and untreated hearts. The capillary density in infarct border zone was significantly higher in the ASC-treated hearts than in the CCM-treated and untreated hearts. However, only 0.5% of the ASCs recovered from the ASC-treated hearts were stained positive for cardiac-specific fibril proteins. It was also found that ASCs under a normal culture condition secreted three cardiac protective growth factors: vascular endothelial growth factor, hepatocyte growth factor, and insulin-like growth factor-1. Results of this study suggest that ASCs were able to improve cardiac function of infarcted rat hearts. Paracrine effect may be the mechanism underlying the improved cardiac function and increased capillary density.

Superparamagnetic iron oxide does not affect the viability and function of adipose-derived stem cells, and superparamagnetic iron oxide-enhanced magnetic resonance imaging identifies viable cells.

The objectives of this study were (1) to determine whether superparamagnetic iron oxide (SPIO) affects viability, transdifferentiation potential and cell-factor secretion of adipose-derived stem cells (ASCs); and (2) to determine whether SPIO-enhanced magnetic resonance (MR) imaging highlights living stem cells. Rat ASCs were incubated in SPIO-containing cell culture medium for 2 days. The SPIO-treated ASCs were then subjected to adipogenic, osteogenic and myogenic transdifferentiation. Expression of vascular endothelial growth factor, hepatocyte growth factor and insulin-like growth factor 1 by the SPIO-treated ASCs was measured using reverse transcription polymerase chain reaction. Cell viability was assessed using trypan blue stain. For in vivo experiments, SPIO-labeled ASCs were injected into 10 rat hearts. The hearts were monitored using MRI. We found that survival rate of the ASCs cultured in the SPIO-containing medium was very high (97-99%). The SPIO-treated ASCs continued to express specific markers for the three types of transdifferentiation. Expression of the cell factors by the ASCs was not affected by SPIO. Signal voids on MR images were associated with the living SPIO-labeled ASCs in the rat hearts. We conclude that SPIO does not affect viability, transdifferentiation potential or cell-factor secretion of ASCs. MRI mainly highlights living SPIO-labeled stem cells.

Alternate antegrade/retrograde perfusion: an effective technique to preserve hypertrophied hearts during valvular surgery.

OBJECTIVE: Continuous antegrade perfusion (AP) may interfere with surgical precision. Continuous retrograde perfusion (RP), on the other hand, cannot sustain the empty-beating hypertrophied hearts. Therefore, alternate antegrade/retrograde perfusion (A(A/R)P) may be a rational technique to preserve the hypertrophied hearts. This study is to determine whether A(A/R)P could maintain myocardial energy metabolism, oxygenation, and contractile function of the empty-beating hypertrophied hearts. METHODS: Sixteen hypertrophied pig hearts were divided into four groups (n=4 per group). Group I and II underwent an 80-min A(A/R)P (four 10-min APs and four 10-min RPs), followed by a 20-min reperfusion. Group III and IV were subjected to an 80-min AP and 20-min reperfusion and used as a control. Energy metabolism was evaluated in group I and III using magnetic resonance spectroscopy. Myocardial oxygenation (MO) was assessed in group II and IV using near infrared spectroscopic imaging. RESULTS: During 80-min A(A/R)P, four episodes of RP resulted in a significant decrease in myocardial phosphocreatine (PCr) and MO. The subsequent AP, however, resulted in complete recovery of the parameters. Moreover, myocardial adenosine triphosphate (ATP) remained at a normal level throughout the 80-min A(A/R)P. As expected, hearts in groups III and IV showed normal level of myocardial PCr, ATP, and MO throughout protocol. Finally, hearts in all four groups showed similar contractile function during reperfusion. CONCLUSIONS: A(A/R)P with four 10-min intervals of AP and RP sustained normal myocardial energy metabolism, oxygenation, and contractile function of empty-beating hypertrophied hearts. We conclude that A(A/R)P is an effective technique for preservation of empty-beating hypertrophied hearts during valvular surgery.

The effects of simultaneous antegrade/retrograde cardioplegia on cellular volumes and energy metabolism.

BACKGROUND AND AIM OF THE STUDY: Simultaneous antegrade/retrograde cardioplegia (SARC) has been employed frequently during cardiac surgery to preserve the jeopardized myocardium. However, retrograde perfusion of SARC may interfere with myocardial drainage and disrupt myocardial fluid homeostasis, which may affect the myocardial energy metabolism and contractile function. The study was, therefore, designed to assess the effects of SARC on myocardial fluid homeostasis, cellular volumes, and energy metabolism. METHODS: Eight isolated pig hearts were subjected to a protocol consisting of a 20-minute control perfusion, 120-minute SARC, and 20-minute reperfusion. The myocardial water content was monitored using near-infrared spectroscopy. Phosphorus-31 magnetic resonance ((31)P MR) spectroscopy was used to monitor the volumes of both intracellular and extracellular compartments and assess myocardial energy metabolism. RESULTS: The near-infrared spectra showed that the 120-min SARC resulted in a 60 +/- 12% increase in the myocardial water content. (31)P MR spectra showed a 36 +/- 4% increase in the intracellular compartment and a 54 +/- 8% increase in the extracellular compartment during SARC relative to their initial volumes measured during control perfusion (100%). However, the myocardial energy metabolites (adenosine triphosphate [ATP] and phosphocreatine [PCr]) remained unchanged during the 120-minute SARC. Moreover, during reperfusion, the hearts showed an almost complete recovery in the left ventricular-developed pressure. CONCLUSIONS: A prolonged SARC resulted in water accumulation in both extracellular and intracellular compartments in the normal myocardium. Although its detrimental effect on tissue fluid homeostasis did not jeopardize the myocardial energy metabolism, a prolonged use of SARC should be avoided, particularly in the diseased hearts.

Identification of chronic myocardial infarction with extracellular or intravascular contrast agents in magnetic resonance imaging.

AIM: To determine whether extracellular or intravascular contrast agents could detect chronic scarred myocardium in magnetic resonance imaging (MRI). METHODS: Eighteen pigs underwent a 4 week ligation of 1 or 2 diagonal coronary arteries to induce chronic myocardial infarction. The hearts were then removed and perfused in a Langendorff apparatus. Eighteen hearts were divided into 2 groups. The hearts in groups I (n=9) and II (n=9) received the bolus injection of Gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA, 0.05 mmol/kg) and gadolinium- based macromolecular agent (P792, 15 micromol/kg), respectively. First pass T2* MRI was acquired using a FLASH sequence. Delayed enhancement T1 MRI was acquired with an inversion recovery prepared TurboFLASH sequence. RESULTS: Wash-in of both agents resulted in a sharp and dramatic T2* signal loss of scarred myocardium similar to that of normal myocardium. The magnitude and velocity of T2* signal recovery caused by wash-out of extracellular agents in normal myocardium was significantly less than that in scarred myocardium. Conversely, the T2* signal of scarred and normal myocardium recovered to plateau rapidly and simultaneously due to wash-out of intravascular agents. At the following equilibrium, extracellular agent-enhanced T1 signal intensity was significantly greater in scarred myocardium than in normal myocardium, whereas there was no significantly statistical difference in intravascular agent-enhanced T1 signal intensity between scarred and normal myocardium. CONCLUSION: After administration of extracellular agents, wash-out T2* first-pass and delayed enhanced T1 MRI could identify scarred myocardium as a hyperenhanced region. Conversely, scarred myocardium was indistinguishable from normal myocardium during first-pass and the steady state of intravascular agents.

Surgery for cardiac valves and aortic root without cardioplegic arrest ("beating heart"): experience with a new method of myocardial perfusion.

Simultaneous antegrade/retrograde warm blood perfusion with a beating heart has not been previously reported as a mean of protecting hypertrophied hearts in cardiac valve and aortic root surgeries. Similarly, beating heart mitral valve surgery via the trans-septal approach with the aorta unclamped, is a novel technique. We, herein, report a series of 346 patients with a variety of cardiac pathologies who were operated upon utilizing a new modality of myocardial perfusion. Among this group of patients, there were 55 patients who were diagnosed with endocarditis of one or more valves. These patients were excluded from this series of patients. Mean age was 59 +/- 12, and there were 196 (67.3%) males and 95 (32.7%) females. There were six aortic root procedures, 90 mitral valve replacements (MVR), 46 mitral valve repairs, 20 MVR+ coronary artery bypass grafting (CABG), 28 tricuspid valve repairs, 106 aortic valve replacements (AVR), 17 AVR+CABG, and 8 AVR/MVR. Crude mortality for the group was 20 of 291 (6.8%). Intra-aortic balloon pump utilization at time of weaning from cardiopulmonary bypass was 6/291 (2.06%), and re-operation for bleeding was needed in 12 of 291 (4.1%) patients. Postoperative stroke occurred in 4 of 291 (1.3%) patients. In these patients, the clinical diagnosis of stroke was made prior to surgery. This initial experience with this new method of myocardial perfusion indicates that results are at least comparable, if not superior, to conventional techniques utilizing intermittent cold blood cardioplegia.

Does normothermic normokalemic simultaneous antegrade/retrograde perfusion improve myocardial oxygenation and energy metabolism for hypertrophied hearts?

BACKGROUND: Beating-heart valve surgery appears to be a promising technique for protection of hypertrophied hearts. Normothermic normokalemic simultaneous antegrade/retrograde perfusion (NNSP) may improve myocardial perfusion. However, its effects on myocardial oxygenation and energy metabolism remain unclear. The present study was to determine whether NNSP improved myocardial oxygenation and energy metabolism of hypertrophied hearts relative to normothermic normokalemic antegrade perfusion (NNAP). METHODS: Twelve hypertrophied pig hearts underwent a protocol consisting of three 20-minute perfusion episodes (10 minutes NNAP and 10 minutes NNSP in a random order) with each conducted at a different blood flow in the left anterior descending coronary artery (LAD [100%, 50%, and 20% of its initial control]). Myocardial oxygenation was assessed using near-infrared spectroscopic imaging. Myocardial energy metabolism was monitored using localized phosphorus-31 magnetic resonance spectroscopy. RESULTS: With 100% LAD flow, both NNAP and NNSP maintained myocardial oxygenation, adenosine triphosphate, phosphocreatine, and inorganic phosphate at normal levels. When LAD flow was reduced to 50% of its control level, NNSP resulted in a small but significant decrease in myocardial oxygenation and phosphocreatine, whereas those measurements did not change significantly during NNAP. With LAD flow further reduced to 20% of its control level, both NNAP and NNSP caused a substantial decrease in myocardial oxygenation, adenosine triphosphate, and phosphocreatine with an increase in inorganic phosphate. However, the changes were significantly greater during NNSP than during NNAP. CONCLUSIONS: Normothermic normokalemic simultaneous antegrade/retrograde perfusion did not improve, but slightly impaired myocardial oxygenation and energy metabolism of beating hypertrophied hearts relative to NNAP. Therefore, NNSP for protection of beating hypertrophied hearts during valve surgery should be used with extra caution.

Keeping the heart empty and beating improves preservation of hypertrophied hearts for valve surgery.

OBJECTIVE: This study was designed to determine whether keeping the heart empty and beating improved myocardial fluid homeostasis and energy metabolism of hypertrophied pig hearts in comparison with cardioplegic arrest. METHODS: Twenty piglets underwent a 8-weeks (corrected) ascending aortic banding to induce left ventricular hypertrophy. Isolated hypertrophied hearts were divided into 4 groups (n = 5 in each group). Two groups underwent normothermic normokalemic simultaneous perfusion. The other 2 groups were subjected to normothermic hyperkalemic simultaneous perfusion and used as controls. Intramyocardial hydrostatic pressure was monitored with a microtip pressure transducer. Volumes of intracellular and extracellular compartments and myocardial energy metabolism were monitored by using phosphorus 31 magnetic resonance spectroscopy. RESULTS: Normothermic normokalemic simultaneous perfusion (NNSP) maintained intramyocardial hydrostatic pressure at a significantly lower level (13.0 +/- 0.6 mm Hg) compared with normothermic hyperkalemic simultaneous perfusion (NHSP) (23.3 +/- 1.2 mm Hg) during a 90-minute preservation. NNSP maintained the normal volume of the intracellular compartment throughout the preservation period, whereas NHSP caused significant enlargement (to 123% +/- 6% of its normal volume) of the intracellular compartment. Expansion of the extracellular compartment during preservation was significantly less in the NNSP group (124% +/- 6%) than in the NHSP group (152% +/- 7%). NNSP maintained normal levels of phosphocreatine and adenosine triphosphate until coronary perfusion flow was reduced to 50% of the initial control level. No decrease in energy metabolites was observed in the NHSP group even when coronary perfusion flow was reduced to 10% of the initial control level. CONCLUSIONS: Keeping the heart empty and beating improves myocardial fluid homeostasis for hypertrophied hearts relative to cardioplegic arrest. Its ability to maintain energy metabolism depends on the degree of coronary stenosis. This technique may be a promising protective strategy for hypertrophied hearts.

Increased pressure during retrograde cerebral perfusion provides better preservation of the Na+, K+-ATPase activity.

This study was carried out to determine if increased perfusion pressure during retrograde cerebral perfusion (RCP) provides better preservation of the brain Na+, K+-ATPase activity. Twenty pigs were subjected to anesthesia alone (control group, n=5), hypothermic circulatory arrest (HCA) (HCA group, n = 5), HCA+RCP at perfusion pressures of 24-29 mmHg (Low-pressure group, n=5), or HCA+RCP at perfusion pressures of 34-40 mmHg (High-pressure group, n = 5). The brain was harvested for the measurement of tissue Na+, K+-ATPase activity. Relative to the control pigs (67.2 +/- 2.1%), significant impairment of Na+, K+-ATPase activity was observed in all three experimental groups (29.8 +/- 7.4% in HCA group, 33.5 +/- 2.9% in the Low-pressure group, and 52.0 +/- 1.8% in the High-pressure group, p < 0.01). The best preservation of the enzyme, particularly in the cortex and cerebellum regions, was observed in the High-pressure group (p < 0.01). In conclusion, HCA causes severe impairment of Na+, K+-ATPase activity, and increasing perfusion pressures from 24-29 to 34-40 mmHg during RCP significantly improves preservation of Na+, K+-ATPase activity, and the improvement of the protection varies in different regions of the brain.

Tissue edema does not change gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA)-enhanced T1 relaxation times of viable myocardium.

PURPOSE: To determine whether tissue edema changes gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA)-enhanced T1 relaxation times of the viable myocardium. MATERIALS AND METHODS: A total of 16 isolated pig hearts were divided into four groups (N=4/group) and perfused in a Langendorff apparatus. Gd-DTPA was injected into the aortic perfusion line. Tissue edema was then induced by two hours of simultaneous arterial/venous perfusion (SAVP). Myocardial water content and T1 relaxation times were monitored throughout SAVP. The volumes of the extracellular and intracellular compartments were assessed using 31P MRS-detectable markers, phenylphosphonic acid (PPA) and dimethyl methylphosphonate (DMMP). RESULTS: Tissue water content in both viable and infarcted myocardium increased significantly during two-hour SAVP. However, Gd-DTPA-enhanced T1 relaxation times of the viable myocardium remained relatively unchanged. Infarcted myocardium, on the other hand, exhibited significant T1 shortening during SAVP. Furthermore, SAVP resulted in significant expansions of both extracellular and intracellular compartments, but the ratio of the volumes of the two compartments remained relatively constant. CONCLUSION: Tissue edema in the viable myocardium does not increase the relative distribution volume of the contrast agent. As a result, edema does not change Gd-DTPA-enhanced T1 relaxation times of the viable myocardium.

Is maintenance of cerebral hypothermia the principal mechanism by which retrograde cerebral perfusion provides better brain protection than hypothermic circulatory arrest? A study in a porcine model.

OBJECTIVE: Retrograde cerebral perfusion (RCP) provides better brain protection than hypothermic circulatory arrest (HCA) alone. The mechanism by which RCP improves brain protection during circulatory arrest remains unknown. The purpose of the study in pigs was to determine if RCP improves brain protection mainly as a result of its ability to maintain cerebral hypothermia. METHODS: Fifteen pigs were subjected to 120 minutes of HCA alone (HCA group, n = 5), HCA + RCP at perfusion pressures of 23 to 29 mmHg (RCP-low group, n = 5), or at perfusion pressures of 34-40 mmHg (RCP-high group, n = 5) at 15 degrees C, followed by 60 minutes of normothermic cardiopulmonary bypass (CPB). After brain temperature reached 15 degrees C, HCA was initiated with or without RCP. Temperatures in the brain, esophagus, and perfusate/blood were monitored continuously. Brain tissue blood flow was measured continuously using a laser flowmeter. Brain oxygen extraction was calculated from the oxygen contents in arterial and venous blood samples. RESULTS: During cooling and rewarming, the change in temperature was slower in the brain than in the esophagus. A similar degree of spontaneous rewarming (from 15 degrees C to 17/18 degrees C) occurred in the brain during HCA and RCP. This indicates that RCP does not provide better maintenance of cerebral hypothermia during circulatory arrest than HCA alone. The esophageal temperature rose more slowly during RCP than during HCA alone, indicating that RCP maintains better hypothermia in the body. During RCP, the brain extracted oxygen continuously from the blood, indicating that RCP may provide nutrient flow to the brain. CONCLUSION: In an acute pig model, maintenance of cerebral hypothermia does not appear to be the principal mechanism by which RCP provides better brain protection than HCA alone. Retrograde cerebral perfusion provides nutrient flow/oxygen to brain tissue, leading to better brain protection than HCA alone.

Mapping myocardial viability using interleaved T1-T2* weighted imaging.

The present study was to evaluate the efficacy of our interleaved T1-T2* weighted imaging for assessing myocardial viability. The left anterior descending coronary artery (LAD) of pig hearts (n = 7) were occluded for 2 h, followed by 1 h reperfusion. After removed from animals, the hearts were perfused in a Langendorff apparatus with a mixture of pig blood and crystalloid solution in 1:1 ratio. T1 relaxation times of the myocardium were measured with a TurboFLASH inversion-recovery sequence. Gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) (0.05 mmol/kg body wt) was then injected as a bolus into the aortic perfusion line. The first pass of the contrast agent through the heart was followed using the interleaved T1-T2* imaging sequence. Once the concentration of the contrast agent was in an equilibrium state, T1 relaxation times were measured again. It was found that the percentage recovery of T2* intensity (PRT2*) at the maximum T1 intensity measured during the first pass of the contrast agent with the interleaved T1-T2* imaging was significantly higher in infarcted myocardium than in normal myocardium. Moreover, the regions showing a high T2* percentage recovery on PRT2* maps matched well with the infarcted myocardium demarcated with triphenyl tetrazolium chloride (TTC) staining. We therefore conclude that infarcted myocardium can be delineated using the interleaved T1-T2* imaging method.

Use of a pH-stat strategy during retrograde cerebral perfusion improves cerebral perfusion and tissue oxygenation.

BACKGROUND: Although it is well documented that the use of a pH-stat strategy during hypothermic cardiopulmonary bypass improves cerebral blood flow, an alpha-stat strategy has been almost exclusively used during retrograde cerebral perfusion. We investigated the effects of pH-stat and alpha-stat management on brain tissue blood flow and oxygenation during retrograde cerebral perfusion in a porcine model to determine if the use of a pH-stat strategy during retrograde cerebral perfusion improves brain tissue perfusion. METHODS: Fourteen pigs were managed by an alpha-stat strategy (alpha-stat group, n = 7) or by a pH-stat strategy (pH-stat group, n = 7) during 120 minutes of hypothermic retrograde cerebral perfusion. Retrograde cerebral perfusion was established through the superior vena cava. Brain tissue blood flow and oxygenation were measured continuously with a laser flowmeter and near infrared spectroscopy, respectively. Brain tissue water content was determined at the end of the experiments. RESULTS: During cooling, brain tissue blood flow was significantly higher with use of the pH-stat strategy than with the alpha-stat strategy (86% +/- 10% versus 40% +/- 3% of baseline). During retrograde cerebral perfusion, brain tissue blood flow was also significantly higher (about three times higher) in the pH-stat group than in the alpha-stat group (15% +/- 4% versus 5% +/- 1% of baseline at 60 minutes of retrograde cerebral perfusion). Tissue oxygen saturation appeared to be higher during retrograde cerebral perfusion in the pH-stat group than in the alpha-stat group. Brain tissue blood flow during rewarming remained significantly higher with the use of pH-stat than with the use of alpha-stat. Brain tissue water contents were similar in both groups. CONCLUSIONS: In our pig model, the use of a pH-stat strategy during retrograde cerebral perfusion significantly improves brain tissue perfusion. Therefore, to improve retrograde cerebral blood flow during retrograde cerebral perfusion, it may be preferable to use a pH-stat strategy, rather than an alpha-stat strategy.

Unclamping the inferior vena cava during retrograde cerebral perfusion increases the safe range of retrograde perfusion pressures and improves brain perfusion.

We investigated the effect of different methods of management of the inferior vena cava (IVC) during retrograde cerebral perfusion (RCP) on the relationships between RCP pressure, regional cerebral blood flow, tissue oxygenation, and intracranial pressure (ICP). Fourteen pigs were subjected to hypothermic (15 degrees C) RCP at RCP pressures varying from 10 to 110 mmHg with clamping (closed group, n=7) or without clamping of the IVC (open group, n=7). Intracranial pressures increased more slowly in the open group than in the closed group and were significantly lower at any level of RCP pressure in the open group than in the closed group. In the closed group, RCP pressures of 20-30 mmHg resulted in an ICP of 25 mmHg. In contrast, in the open group, when RCP pressures were maintained below 70 mmHg, ICP never reached 25 mmHg. Brain tissue blood flow and CO2 production were relatively higher in the open group than in the closed group. The maximum brain tissue blood flow was achieved at an RCP pressure of 40 mmHg in the open group. We conclude that the maximum safe RCP pressure differs according to the type of management of the IVC. Opening the IVC during RCP not only improves brain tissue perfusion, but also significantly increases the safety margin of RCP pressures. In the pig model, when the IVC is not clamped, the optimal RCP pressure appears to be 40 mmHg.

Retrograde cardioplegia.

OBJECTIVE: This study was undertaken to compare the efficacy of retrograde cardioplegia for myocardial perfusion with that of antegrade cardioplegia at the same flow rate. METHODS: Colored microspheres were used in rat hearts to assess the capillary flow of cardioplegia solution. Myocardial perfusion was evaluated with magnetic resonance imaging in pig hearts. Phosphorus 31 magnetic resonance spectroscopy was used to determine the efficacies of the cardioplegic techniques in sustaining myocardial energy metabolism. RESULTS: At the same flow rate, the number of colored microspheres delivered to the capillaries by retrograde cardioplegia (15 +/- 1 microspheres/mm2) was significantly lower than that delivered by antegrade cardioplegia (29 +/- 2 microspheres/mm2). Furthermore, only 19% +/- 3% of the colored microspheres delivered to the capillaries by retrograde cardioplegia were found in the arteriolar portions of the capillaries, whereas most (80% +/- 3%) remained in the venular portions. Moreover, magnetic resonance images showed that contrast-enhanced signal-time courses obtained from different regions of the myocardium during retrograde cardioplegia varied significantly. Localized phosphorus 31 spectra showed that retrograde cardioplegia required a higher flow rate than did antegrade cardioplegia to sustain normal myocardial energy metabolism. CONCLUSIONS: We conclude that retrograde cardioplegia provides significantly less capillary flow than does antegrade cardioplegia. Its microvascular perfusion varies significantly among the various small areas of the myocardium. As a result, its efficacy in sustaining normal myocardial energy metabolism is lower than that of antegrade cardioplegia.

Increased pressure during retrograde cerebral perfusion in an acute porcine model improves brain tissue perfusion without increase in tissue edema.

BACKGROUND: There is a significant lack of scientific data to support the clinically accepted view that 25 to 30 mm Hg is the maximum safe perfusion pressure during retrograde cerebral perfusion (RCP). This study was designed to investigate whether perfusion pressure greater than 30 mm Hg during RCP is beneficial to the brain during prolonged HCA in an acute porcine model. METHODS: Sixteen pigs underwent 120 minutes of circulatory arrest in conjunction with RCP at a perfusion pressure of either 23 to 29 mm Hg (group L, n = 8) or 34 to 40 mm Hg (group H, n = 8) at 15 degrees C, followed by 60 minutes of normothermic cardiopulmonary bypass. Cortical blood flow and oxygenation were measured continuously with a laser flowmeter and near-infrared spectroscopy, respectively. Tissue water content was measured at the end of the experiments. RESULTS: Brain tissue blood flow was significantly higher in group H than in group L (16.8% +/- 4.1% vs 4.8% +/- 0.9% of baseline, p < 0.01) during RCP. Brain oxygen extraction in group L reached a maximum (approximately 70%) immediately after starting RCP, whereas in group H it increased gradually and reached a maximum at 120 minutes of RCP, indicating a greater supply of oxygen to tissue in group H than in group L. After RCP, the ability of brain tissue to use oxygen was better preserved in group H than in group L, as indicated by tissue oxygen saturation and the deoxyhemoglobin level. There was no significant increase in tissue water content in either group (group H 79.2% +/- 0.3%, group L 79.1% +/- 0.4%) relative to normal control pigs (78.7% +/- 0.1%). CONCLUSIONS: In this acute porcine model, increasing perfusion pressure from 23-29 to 34-40 mm Hg during RCP increases tissue blood flow and provides better tissue oxygenation, without increasing tissue edema. The optimal perfusion pressure for RCP needs to be further investigated.

Simultaneously monitoring both T(1) and T(2)* signal intensities on a bolus injection of Gd-DTPA may distinguish infarcted myocardium.

PURPOSE: To determine whether injured myocardium may be identified by simultaneously monitoring contrast-induced T(1) and T(2)* signal intensity time-course changes with an interleaved T(1)-T(2)* imaging sequence. MATERIALS AND METHODS: Gadolinium-diethylene triamine pentaacetic acid (0.05 mmol/ kg) was injected as a bolus into ex vivo pig hearts, and simultaneous T(1) and T(2)* time-courses were obtained during the first pass. RESULTS: Observing contrast-enhanced R(1) or R(2)* rates (1/T(1) or 1/T(2)* times, respectively) early after contrast injection did not fully differentiate viable from nonviable myocardium. T(2)* recovery at maximal T(1) signal intensity, measured using simultaneous T(1) and T(2)* imaging, displayed a significantly different percentage recovery (P < 0.05) among normal (30.5 +/- 2.4% of baseline value), reperfused infarcted (63 +/- 7.2%), and low-reflow infarcted (90 +/- 2.8%) myocardium. CONCLUSION: Simultaneously monitoring both T(1) and T(2)* signal intensities may help in the assessment of myocardial injury.