Refinement of the alpha aminooleic acid bioprosthetic valve anticalcification technique.

BACKGROUND: Aminooleic acid treatment has been demonstrated to prevent porcine valve calcification and to protect valvular hemodynamic function. Initial enthusiasm was tempered by histologic studies of these AOA valves, which showed cuspal hematomas, structural loosening, and surface roughening. This prompted a systematic review of the AOA treatment process. Unsolubilized particles of alpha aminooleic acid present in the treatment solution were identified as the cause of mechanical abrasion of valve cusps during processing. These particles were eliminated with a revamped protocol, which included filtration of the AOA solution before valve preparation. METHODS: Porcine aortic valve cusps treated with this modified AOA protocol (AOA II) were studied in a rat subdermal implant model of mineralization. A juvenile sheep trial was then used to confirm the antimineralization effects of AOA II on glutaraldehyde-fixed porcine aortic roots in a circulatory model of accelerated calcification. RESULTS: Retrieved AOA II-treated cusps from the subdermal model were markedly less calcified than control cusps (AOA II, 1 +/- 0, 17 +/- 4, 23 +/- 6, and 17 +/- 10 versus control, 189 +/- 14, 251 +/- 16, 250 +/- 14, and 265 +/- 10 mg calcium/mg sample at 4, 8, 12, and 16 weeks, respectively; p < 0.0001). Morphologic examination of the AOA II cusps of the valves retrieved from the sheep demonstrated freedom from the structural loosening, surface roughening, and hematoma formation that had limited the utility of the original AOA preparation technique. Cusps from AOA II-treated porcine roots had significantly less calcium than control cusps (AOA II, 5.5 +/- 3.0 mg/g; control, 91.2 +/- 19.5 mg/g; p = 0.0004). The aortic walls had similar levels of calcification (AOA II, 156 +/- 73 mg/g; control, 159 +/- 10 mg/g; p = not significant). CONCLUSIONS: These data suggest that the modified AOA technique warrants further evaluation as an antimineralization treatment for glutaraldehyde-fixed porcine bioprostheses.

Hemodynamic significance of the coronary vein valves.

The incidence and morphology of one-way coronary vein valves were studied, together with their influence on the administration of retrograde cardioplegia. Calf, juvenile pig, and adult mongrel canine hearts (12 each) and human cadaver hearts (five adult and seven pediatric) were dissected. The pressure gradients between the coronary sinus and the posterior vein of the left ventricle were measured in 21 hearts during the retrograde administration of fluid. Species differences were noted, with apparently competent valves seen more frequently in calf hearts (mean, 1.33 valves +/- 0.22 [SEM] per heart) than in pig hearts (mean, 0.83 +/- 0.17 [SEM] per heart). In humans, more valves were seen in pediatric hearts (five valves in seven hearts) than in adult hearts (one valve in five hearts). No competent valves were found in dog hearts (chi 2 analysis; p < 0.0001). In calf hearts, a pressure gradient of 5 to 35.5 mm Hg was required before the valve opened. In pig hearts, these opening pressure gradients ranged from 0 to 19.5 mm Hg. The distribution of retrograde cardioplegia may be impaired in the presence of competent valves, particularly when low coronary sinus pressures are used.

Warm blood cardioplegia: superior protection after acute myocardial ischemia.

Three myocardial protection techniques were studied in a canine model of acute myocardial ischemia with subsequent revascularization. Eighteen animals were randomly assigned to one of three treatment regimens: cold oxygenated crystalloid cardioplegia (CC), cold blood cardioplegia with modified reperfusate (CB), and continuous aerobic warm blood cardioplegia (WB) (n = 6 per group). Systemic hypothermic cardiopulmonary bypass (28 degrees C), antegrade arrest, and intermittent retrograde and antegrade delivery were used for the CC and CB groups. Systemic normothermic cardiopulmonary bypass, antegrade arrest, and continuous retrograde delivery were used for the WB group. Fifteen minutes of warm global ischemia was followed by occlusion of the left anterior descending coronary artery (15-minute duration) and simultaneous initiation of cardioplegic arrest (60-minute duration) to simulate clinical revascularization. After reperfusion, the animals were separated from cardiopulmonary bypass. Myocardial function, electrocardiogram, myocardial energetics, water content, histopathology, and defibrillation requirements were compared between groups. There was no significant difference in maximum elastance, myocardial oxygen consumption, myocardial edema, or histopathologic evidence of injury between groups. However, overall ventricular function, assessed by the slope of the preload recruitable stroke work relationship, was significantly better for the WB group (p = 0.04) (WB, 73 +/- 9; CB, 56 +/- 7; CC, 47 +/- 5). Diastolic function as assessed by the slope of the stress-strain relationship was significantly worse overall for the cold groups (p = 0.001) (WB, 20 +/- 2.2; CB, 39 +/- 1.3; CC, 37 +/- 3.1). Myocardial injury as assessed by ST segment elevation (millimeters) was less for the WB group (p = 0.03) (WB, 0.4 +/- 0.3; CB, 1.7 +/- 0.2; CC, 1.6 +/- 0.7). Countershocks necessary to restore sinus rhythm after cross-clamp removal were fewer in the WB group (p = 0.03) (WB, 0.8 +/- 0.3; CB, 4.0 +/- 1.2; CC, 5.5 +/- 1.5). In this model of acute global myocardial ischemia, continuous aerobic warm blood cardioplegia has important advantages over two widely used clinical hypothermic protection techniques.

Cardioplegia for heart transplantation: unmodified UW solution compared with Stanford solution.

Clinical practice and laboratory studies have demonstrated the efficacy of cold crystalloid cardioplegia for donor heart protection. Efforts to increase the margin of safety for protection led us to compare unmodified University of Wisconsin (UW) solution to the dextrose, mannitol-based Stanford (ST) solution. A canine model of heart transplantation with antegrade hypothermic cardioplegic arrest and 6 hours of 4 degrees C ischemic storage was used. An oxygenated blood-primed isolated heart preparation was used for reperfusion and myocardial mechanics and energetics studies of the working heart. Six of 6 UW and 4 of 6 ST hearts reached the working phase. Computer-assisted analysis of pressure-volume loops generated at varying flows measured by tri-axial sonomicrometry and high-fidelity micromanometry showed no significant differences in function between the ST and UW groups by maximum elastance (UW, 4.2 +/- 1.1; ST, 4.0 +/- 0.7), preload recruitable stroke work (UW, 43.7 +/- 7.3; ST, 43.4 +/- 8.7), or slope of log-linear end-diastolic pressure-volume curve (UW, 0.057 +/- 0.01, ST, 0.061 +/- 0.01). Specimens for determination of myocardial water content were taken after cardioplegic arrest, after storage, after reperfusion, and after the working phase. There was a significant increase in tissue water after reperfusion in both groups (UW, 75.7% +/- 0.5% to 81.6% +/- 0.2%, p = 0.0001; ST, 76.5% +/- 0.4% to 83.4% +/- 0.3%, p = 0.0002), which persisted after the working phase (UW, 81.5% +/- 0.9%, p = 0.0002; ST, 82.6% +/- 0.1%, p = 0.0003). Both groups exhibited postreperfusion increase in myocardial water content, but this edema was significantly less marked in the UW group (p = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Calcification of porcine valves: a successful new method of antimineralization.

Despite distinct advantages over mechanical cardiac valve prostheses, the use of bioprosthetic valves remains limited due to poor long-term durability, primarily as a result of tissue calcification. A novel anticalcification process, based on treatment of porcine bioprostheses with a derivative of oleic acid, has been developed by one of us (J.M.G.) (US Patent Number 4,976,733). This process employing 2-aminooleic acid (AOA) was tested in a juvenile sheep model. Terminal studies after a 20-week interval included hemodynamic, radiographic, morphologic, and quantitative tissue calcium analyses. All control valves (n = 4) had thickened, immobile, heavily calcified leaflets, whereas all AOA-treated valves (n = 8) were pliable and free of calcium deposits. Calculated valve orifice areas for controls (0.9 +/- 0.2 cm2) (mean +/- standard error of the mean) was less than for AOA-treated valves (2.0 +/- 0.3 cm2) (p less than 0.05). Radiographic calcification scores were greatly elevated in the control (25.5 +/- 5.6) versus AOA-treated valves (0.5 +/- 0.5) (p less than 0.002). In quantitative mineralization studies, the mean calcium content of the control leaflets was 129 +/- 21 milligrams per gram dry weight cusp tissue versus 7.7 +/- 5.8 mg/g for AOA-treated valves (p less than 0.001). Pathologic examination confirmed heavy calcification in the control leaflets, which was essentially absent in the AOA-treated leaflets. However, cuspal hematomas in areas of structural loosening and surface roughening were noted in AOA-treated valves. This anticalcification process dramatically reduced mineralization of porcine valve prostheses in this model.

Placement of aortic valve bioprostheses in sheep via a left thoracotomy. Implantation of stentless porcine heterografts.

Juvenile sheep provide a good model for assessing the efficacy of antimineralization techniques because of their rapid calcification of bioprosthetic valves. Stentless bioprosthetic valves are under evaluation for possible improved durability as aortic valve replacements. A left thoracotomy approach for aortic valve implantation, which facilitates intraoperative and postoperative hemodynamic data collection, has been developed and refined in 13 sheep. A critical feature of this technique is a partial rib resection that creates a soft tissue acoustic window to improve postoperative transthoracic echocardiographic examination. This allows both quantification of valvular gradients and qualitative assessment of valve leaflet motion and calcification. Excellent correlation was observed between the intraoperative invasive valvular gradients and the postoperative echocardiographic gradients available in four animals (mean gradient r = 0.96, p = 0.003; peak gradient r = 0.98, p = 0.0004). This is an excellent technique for serial postoperative noninvasive evaluation of valve prostheses implanted in the aortic position.

Cardioplegia for transplantation: failure of extracellular solution compared with Stanford or UW solution.

Crystalloid cardioplegia with an extracellular fluid formulation is widely used for donor heart protection. A survey of 109 transplant programs yielded 62 replies with 42% of respondents using variations of extracellular solution and 45% using the dextrose and mannitol-based Stanford solution. These two commonly used clinical solutions and University of Wisconsin (UW) solution, which has had success in clinical hepatic and renal transplantation, were compared in a canine model of cardiac transplantation. After antegrade hypothermic cardioplegic arrest, the experimental hearts were excised and stored at 4 degrees C for 6 hours (n = 29). An oxygenated, blood-primed isolated heart preparation was used for reperfusion. After a rest of 45 minutes, cardiac output was increased against constant afterload until a left atrial pressure of 15 mm Hg was reached. The maximum cardiac performance measured by cardiac index, minute work, and stroke work was highly significantly better with Stanford or UW solution protection than with the extracellular solutions (p less than 0.0001). Assuming a cardiac index of 50 mL.kg-1.min-1 is necessary for successful separation from cardiopulmonary bypass, only 1 of 14 extracellular and 15 of 15 Stanford and UW animals would have survived (p less than 0.0001). This study strongly suggests that extracellular cardioplegia is inferior for cardiac transplantation and that programs using this solution should reevaluate their method of myocardial protection for donor hearts.

Reperfusion of infarcting myocardium: benefit of surgical reperfusion in a chronic model.

Surgical reperfusion of experimental infarction leads to improved recovery of regional function compared with medical reperfusion, but sustained myocardial salvage has not been demonstrated. Twenty-two dogs were subjected to two hours of anterior descending occlusion and divided into three groups: group P (n = 7), no reperfusion; group M (n = 8), medical reperfusion; and group S (n = 7), controlled surgical reperfusion. Ischemia caused systolic bulging (-36% of control systolic shortening, p less than 0.01) and decreased regional work (9% of control pressure-length loop area, p less than 0.05). Thirty minutes after reperfusion group M had persistent systolic bulging (-9% of control systolic shortening) and decreased regional work (9% of control pressure-length loop area), whereas group S had +17% of control systolic shortening and 33% of control pressure-length loop area. After 1 week, regional function improved in all three groups (percent of control systolic shortening: group P, 26%; group M, 19%; group S, 52%), but systolic shortening was significantly better in group S (p less than 0.05 versus group M). Surgical reperfusion also resulted in one half of the eventual myocardial necrosis found in the other groups (group P, 45% of area at risk; group M, 38%; group S, 19%; p less than 0.05, group S versus group P or M). In this model, medical reperfusion offered no demonstrable benefit, whereas controlled surgical reperfusion led to a sustained (1 week) improvement in regional function and significant myocardial salvage.

Neuropeptide-Y. A peptide found in human coronary arteries constricts primarily small coronary arteries to produce myocardial ischemia in dogs.

Neuropeptide-Y (NPY), a brain peptide, is located in the walls of human coronary arteries. This study assessed the effects of NPY on the coronary circulation in 40 chloralose-anesthetized, open-chest dogs. Intracoronary NPY (42 nmol over 5.2 min) caused a 39% reduction in coronary blood flow without changing heart rate or aortic pressure. To determine whether this vasoconstriction could produce ischemia, intramyocardial pH was measured in seven dogs (group I) and decreased from 7.45 +/- 0.06 to 7.37 +/- 0.06 pH units after NPY in the subendocardium (P less than 0.0002), and from 7.45 +/- 0.06 to 7.40 +/- 0.05 pH units (P less than 0.04) in the subepicardium of the infused zone. Left ventricular ejection fraction (LVEF), measured by radionuclide angiography, decreased from 0.52 +/- 0.08 to 0.42 +/- 0.12 U (n = 5, P less than 0.01) during NPY. NPY-induced vasoconstriction was also associated with ST-T wave changes on the electrocardiogram (ECG) in eight of nine other animals (group V). In another group of six dogs (group IV), the change in small vessel resistance accounted for 94% of the increase in total resistance, so that the primary vasoconstrictor effect of NPY was exerted on small coronary arteries. Thus, NPY, a peptide found in human coronary arteries, caused constriction of primarily small coronary arteries that was severe enough to produce myocardial ischemia as determined by ECG ST-T wave changes, and decreases in intramyocardial pH and LVEF in dogs.

A valveless counterpulsation left ventricular assist pump in the descending aorta: hemodynamic benefit with a reduced risk of cerebral emboli.

Because of valve malfunction and cerebral embolism reported with use of the total artificial heart, the descending aorta was reexamined as a site for a valveless counterpulsation left ventricular assist pump. The pump was introduced into the thoracic aorta at the level of the eight thoracic vertebra in 11 canine right-heart bypass preparations. Heart rate (110 beats per minute), stroke volume (20 ml), and mean arterial pressure (80 or 100 mm Hg) were precisely controlled. The pump ejection volume was adjusted to equal 1 time or 2 times the stroke volume of the dog. A 20-ml ejection led to an 11% reduction in left atrial pressure, an 11% reduction in peak left ventricular pressure, and a 20% reduction in tension time index (all, p less than .05 at a mean arterial pressure of 80 mm Hg). Systolic shortening (ultrasonic crystals) increased by 5% (p less than .05 at a mean arterial pressure of 80 mm Hg). A 40-ml pump ejection led to an 11% reduction in mean left atrial pressure, a 17% reduction in peak left ventricular pressure, and a 21% reduction in tension time index (all, p less than .05 at a mean arterial pressure of 80 mm Hg). The systolic shortening increased by 15% (p less than .05). To assess the relative risk of cerebral embolism, albumin spheres (40 to 60 micrograms) labeled with technetium-99 were injected into the pump chamber in 5 dogs (40-ml ejection, 2.1 +/- 0.1 times the dog's stroke volume).(ABSTRACT TRUNCATED AT 250 WORDS)

Vasoactive drug effects on blood flow in internal mammary artery and saphenous vein grafts.

The internal mammary artery is a dynamic coronary graft, whereas the saphenous vein graft is passive. Therefore, potential exists not only for beneficial vasodilation but also for catastrophic spasm of the artery. The purpose of this study was to examine blood flow in the internal mammary and saphenous vein grafts during infusion of drugs that are commonly used after cardiac operations. A canine right heart bypass preparation allowed precise control of cardiac output, blood pressure, and heart rate, which were maintained constant during drug infusion. Both the internal mammary and saphenous vein grafts were constructed so that they perfused the same coronary bed: They were anastomosed in a Y fashion to a ligated anterior descending coronary artery. Electromagnetic flow probes measured graft flow (with the other graft occluded) before and after 15 minutes of drug infusion. The order of drug infusion was randomized and changes were compared by tests for paired differences. Phenylephrine (2 micrograms/kg/min) decreased flow in both the internal mammary and saphenous vein grafts, whereas norepinephrine (0.1 microgram/kg/min) increased flow in both grafts. Epinephrine (0.05 microgram/kg/min) increased mammary artery flow 16% +/- 6% but decreased saphenous vein graft flow 9% +/- 7%. Nitroglycerin (1 microgram/kg/min) significantly increased internal mammary flow (36% +/- 13%), from 47 +/- 7 to 59 +/- 7 ml/min (p less than 0.01), whereas flow decreased significantly in the saphenous vein graft 14% +/- 3%, from 64 +/- 9 to 59 +/- 8 ml/min (p less than 0.01). Nitroprusside (1 microgram/kg/min) decreased mammary artery flow 12% +/- 2%, from 50 +/- 7 to 44 +/- 7 ml/min (p less than 0.01), but increased saphenous vein graft flow 25% +/- 8%, from 64 +/- 9 to 77 +/- 7 ml/min (p less than 0.01). All hemodynamic variables were unchanged, except for norepinephrine, which significantly increased the first derivative of left ventricular pressure. The results suggest that flow through the canine internal mammary artery is changed by the drugs commonly used in perioperative management. Epinephrine and nitroglycerin increased internal mammary artery flow and decreased saphenous vein graft flow, whereas nitroprusside had the opposite effect. The vascular reactivity of the internal mammary artery must be considered when these drugs are used after coronary revascularization.

Functional consequences and intracoronary localization of alpha-adrenergic stimulation of the canine coronary circulation.

Although alpha-adrenergic stimulation can increase coronary vascular resistance, it remains unknown whether the vasoconstriction can override intrinsic coronary regulatory influences to produce ischemia. Methoxamine, 2 to 4 mg, was infused into the circumflex coronary artery of 23 chloralose-anesthetized open chest dogs, and resulted in a 68% increase in coronary vascular resistance. The functional consequence of this increased coronary vascular resistance was assessed by gated radionuclide ventriculography and ST-T wave changes on the electrocardiogram. In six dogs (Group I), aortic pressure changed trivially (less than 5 mm Hg) to allow distinction between direct effects of the flow reduction and indirect effects of increased aortic pressure. In this group, coronary blood flow decreased 33% from a control value of 44 +/- 10 ml/min (p less than 0.001) and left ventricular ejection fraction decreased from 0.54 +/- 0.12 to 0.46 +/- 0.10 (p less than 0.025). In eight dogs (Group II) in which aortic pressure increased by more than 5 mm Hg, left ventricular ejection fraction decreased from 0.46 +/- 0.07 to 0.39 +/- 0.09 (p less than 0.002). Pressure gradients were measured between the aorta and a distal coronary artery branch to calculate small and large vessel resistances separately in four other dogs (Group III). The resistance of small coronary arteries accounted for 92% of the total increase in coronary vascular resistance produced by methoxamine. In five other dogs (Group IV), intracoronary methoxamine, 2 mg, produced ST-T wave changes suggestive of ischemia as it increased coronary vascular resistance by 33%.(ABSTRACT TRUNCATED AT 250 WORDS)

Improved myocardial recovery after cardioplegic arrest with an oxygenated crystalloid solution.

Possible enhancement of myocardial protection by oxygenation of a crystalloid cardioplegic solution was evaluated in a three-part study. In Part I, canine hearts underwent ischemia followed by heterogeneous cardioplegic arrest for 45 to 60 minutes. Oxygenation led to improved recovery in the left anterior descending region (47% versus 86% recovery, p less than 0.05) (15 minutes of ischemia) and in the circumflex region (9.5% versus 52% recovery, p less than 0.05) (30 minutes of ischemia). Part II was a blind prospective randomized study in 12 patients. It examined creatine kinase, myoglobin, and lactate as well as coronary sinus flow, oxygen consumption, and cardiac work 1 hour after aortic cross-clamping during atrial and during ventricular pacing. No significant difference was demonstrable between control and oxygenated solutions. In Part III, 57 coronary bypass patients were protected with a nonoxygenated solution while 94 patients received an identical oxygenated solution. Twelve-hour creatine kinase levels were similar in the nonoxygenated (9.5 +/- 16 IU, +/- standard deviation) and oxygenated (11 +/- 22 IU) groups if the cross-clamp interval was 28 minutes or less. In patients subjected to longer than 28 minutes of arrest, the 12 hour creatine kinase MB levels were more than twice as high in the nonoxygenated group (26.5 +/- 26 IU) compared to the oxygenated group (9.9 +/- 14 IU, p less than 0.05). In this canine model of heterogeneous cardioplegia and in the routine conduct of coronary bypass operations, oxygenated crystalloid cardioplegia is superior to an identical nonoxygenated solution.

The broadly based pericardial flap. A tissue for atrial wall replacement that grows.

The repair of many congenital heart anomalies would be facilitated by a tissue replacement for the atrial wall or pulmonary artery which would grow with the child. Such a tissue has not previously been identified. In 12 puppies a broadly based flap of pericardium was sutured over the right atrial free wall. The atrial wall was excised from beneath the flap. In four animals the flap was then cut away from its pericardial attachments superiorly, inferiorly, and along the phrenic nerve, leaving an autogenous pericardial patch. In the other eight animals the flap was left intact, allowing retention of neural and vascular supply. The animals were put to death 263 +/- 23 days later. In four animals having a pericardial patch, the area of the patch did not increase (94% of original size, NS) despite an increase in body surface area (BSA) to 169% (p less than 0.05) of original BSA. In eight animals with a pericardial flap, the area of the flap increased to 214% (p less than 0.01) of the original size with an increase in BSA to 199% (p less than 0.01) of original BSA. The flap size index (size/BSA) increased to 109% of the original index while the patch size index decreased to 54% of the original, a significant difference (p less than 0.01). The broadly based pericardial flap grew in a manner parallel to BSA increase in these puppies.

Alterations in regional myocardial function after heterogeneous cardioplegia.

Coronary stenoses lead to heterogeneous delivery of cardioplegic solution during cardiac operations. This situation was simulated by occlusion of the circumflex artery during cardioplegic infusion in canine right heart bypass preparations. Regional myocardial function (systolic shortening by sonomicrometer) was often diminished, despite preservation of global function. The correlation between recovery of circumflex regional function and recovery of stroke work or dP/dt (at constant aortic pressure, heart rate, and left atrial pressure) was poor (r = 0.17 and 0.07). The response of damaged regions to hemodynamic manipulations was studied. Increases in afterload after arrest did not lead to further deterioration of damaged regions. Volume loading (cardiac output 2 to 5 L/min) improved regional function even in severely damaged, bulging regions (p less than 0.05). Regional distensibility (delta length/delta left atrial pressure) decreased by 41% (p less than 0.02) in regions with poor protection and by 22% (p less than 0.01) in regions with good cardioplegic protection. There was also an increase in resting length (p less than 0.001) in both circumstances (5.2% and 3.7%). These changes in diastolic properties have not always been apparent in other experimental studies with less precise hemodynamic control. Heterogeneous cardioplegia causes heterogeneous changes in both diastolic distensibility and systolic function. These changes are poorly detected by examination of global ventricular function.

Calcium-channel blockade as an adjunct to heterogeneous delivery of cardioplegia.

The clinical situation of heterogeneous cardioplegia was simulated in a canine model by temporary ligation of the circumflex coronary artery during a three-hour interval of cardioplegic arrest. Nifedipine and lidoflazine, administered prior to aortic clamping, were evaluated as adjuncts to cold (2 degrees C) crystalloid cardioplegia. Assessment was made of regional function (sonomicrometer systolic shortening) and of global function by measuring left atrial (LA) pressure at constant cardiac output (CO), aortic pressure, and heart rate, and by measuring stroke work at constant LA pressure, aortic pressure, and heart rate. Among 14 control dogs, only 7 could achieve a CO of 5 liters per minute following cardioplegic arrest. Left anterior descending coronary arterial systolic shortening recovered to only 86% of prearrest values (p less than 0.05), circumflex coronary arterial systolic shortening recovered only 28% (p less than 0.01), stroke work recovered 59% (p less than 0.01), and LA pressure was 6.7 mm Hg higher (p less than 0.01) than prior to cardioplegic arrest. Lidoflazine provided no statistically significant benefit in these animals (N = 4). However, dogs given nifedipine (N = 6) had very little change in left anterior descending coronary arterial systolic shortening (99% recovery), stroke work (93% recovery), and LA pressure (delta = 0.4 mm Hg). None of these changes was statistically significant. There was some deterioration in circumflex coronary arterial systolic shortening (56% recovery; p less than 0.05). All 6 dogs given nifedipine achieved a CO of 5 L/min following cardioplegic arrest. Clinical cardioplegia is typically heterogeneous cardioplegia. Calcium-channel blockade appears to be useful in this situation.

Pretreatment with lidoflazine, a calcium-channel blocker. Useful adjunct to heterogeneous cold potassium cardioplegia.

Ten mongrel dogs were studied to determine if pretreatment with lidoflazine would protect the canine myocardium during aortic cross-clamping when circumflex coronary artery occlusion limits the distribution of cold potassium cardioplegia. A canine right heart bypass preparation was used. Regional function was determined with a sonomicrometer. Twenty minutes before aortic cross-clamping, lidoflazine or solvent was administered in a random, blind fashion. A circumflex artery snare prevented the cardioplegic solution from entering the circumflex artery. A 100 minute arrest period with cardioplegic infusion every 20 minutes was followed by 45 minutes of reperfusion before global and regional function were reevaluated. In the group receiving solvent, postarrest function in the circumflex region recovered to only 30% of prearrest values (p less than 0.05), a marked functional deterioration. In the group protected by lidoflazine, function in the circumflex region returned to 90% of prearrest values (NS). Function in the left anterior descending (LAD) regions of both groups demonstrated full recovery after arrest. Global left ventricular function was well preserved in both groups and failed to reflect the damaged, malfunctioning region in the group receiving solvent. These findings suggest that pretreatment with lidoflazine can improve myocardial protection when delivery of cardioplegia is not homogeneous.

Cardioplegic infusion: the safe limits of pressure and temperature.

In patients with coronary artery disease, infusion of very cold cardioplegic solutions at elevated pressures may facilitate homogeneous cooling and cardioplegia. This study was designed to determine if very high infusion pressures or very low temperatures of the cardioplegic solution damages normal myocardium. In a hemodynamically controlled canine right heart bypass preparation, a crystalloid solution (Plasma-Lyte 148 with 30 mEq/L potassium chloride, 0 degree to 2 degrees C) was infused with separate control of the infusion pressures in the left anterior descending and circumflex arteries. A sonomicrometer measured regional myocardial function in each area. During a 100 minute arrest period, cardioplegic solution was reinfused every 20 minutes and reduced myocardial temperatures to an average of 9.4 degrees +/- 2.2 degrees C. In a comparison of infusion pressures of 50 versus 100 mm Hg and 100 versus 150 mm Hg, postarrest regional myocardial function was unchanged from prearrest. However, in a comparison of infusion pressures of 150 to 200 mm Hg, a significant fall in regional myocardial function was noted with the higher pressures (106% and 64% recovery, respectively, p less than 0.02, n = 6). Excluding the areas perfused at 200 mm Hg, comparison of regions cooled to less than 8 degrees C and to greater than 8 degrees C demonstrated no difference in recovery of regional myocardial function. In this study, elevation of cardioplegic infusion pressures to 150 mm Hg and lowering of myocardial temperatures to less than 8 degrees C caused no impairment of regional myocardial function.