Reserve-driven flow control for extracorporeal life support: proof of principle.

Extracorporeal life support systems lack volume-buffering capacity. Therefore, any decrease in venous intravascular volume available for drainage may result in acutely reduced support flow. We recently developed a method to quantify drainable volume and now conceived a reserve-driven pump control strategy, which is different from existing pressure or flow servo control schemes. Here, we give an outline of the algorithm and present animal experimental data showing proof of principle. With an acute reduction in circulatory volume (10-15%), pump flow immediately dropped from 4.1 to 1.9 l/min. Our pump control algorithm was able to restore bypass flow to 3.2 l/min (about 80% of the original level) and, thereby, reduced the duration of the low-flow condition. This demonstrates that a reserve-driven pump control strategy, based on the continuous monitoring of drainable volume, may maintain extracorporeal circulatory support flow, despite serious changes in filling conditions.

Sustained local drug delivery from a radiopaque implanted reservoir.

A new polymeric biomaterial that contains covalently bound iodine, and is therefore radiopaque, was used to construct a sustained local drug-delivery device. A polymeric wall was designed to be porous (i.e., passage of low-molecular-weight molecules across the wall is possible), self-healing, and biocompatible. Once implanted, the sphere cavity can be filled and refilled with a concentrated solution of a (cytostatic) drug, which is subsequently released by slow diffusion into the tissue region surrounding the sphere. This principle of sustained local drug delivery is shown by a series of in vitro experiments on the release of 5-fluorouracil, and in vivo animal experiments, using x-ray fluoroscopic and scintigraphic techniques.

Long-term follow-up (12 to 35 weeks) after dynamic cardiomyoplasty.

OBJECTIVES: To obtain information on the long-term effects of dynamic cardiomyoplasty on hemodynamics and muscle histology, this surgical method was evaluated in goats. BACKGROUND: Dynamic cardiomyoplasty has been introduced as a new method to treat patients with severe cardiac failure. METHODS: In 24 goats, the left latissimus dorsi muscle was wrapped around the heart. The muscle was then subjected to progressive electrical stimulation. In 16 goats, invasive transesophageal Doppler echocardiographic measurements and histologic evaluation of the latissimus dorsi muscle were performed at > or = 12 weeks after the wrapping. RESULTS: Only two goats showed an increase in aortic and left and right ventricular pressures concomitant with increased aortic flow during latissimus dorsi muscle stimulation both before and after induction of cardiac failure using imipramine. This was accompanied by a preserved latissimus dorsi muscle structure and nearly complete transformation to type I muscle fibers. The remaining 14 goats showed extensive lipomatosis in the latissimus dorsi muscle, with severe intimal hyperplasia and proliferation of smooth muscle cells in the walls of the thoracodorsal artery and its branches. An increase in endoneural and endomysial connective tissue was observed, with some goats showing destroyed nerve branches near the electrodes. These findings differed from those observed after long-term electrical stimulation of goat latissimus dorsi muscle in situ. CONCLUSIONS: Dynamic cardiomyoplasty is of use in the treatment of severe heart failure if the histologic structure of the wrapped latissimus dorsi muscle remains intact. Long-term results in goats suggest that the current approach used in dynamic cardiomyoplasty may lead to deterioration of the wrapped muscle.

Acute and short-term effects of partial left ventriculectomy in dilated cardiomyopathy: assessment by pressure-volume loops.

OBJECTIVES: The aim of this study was to evaluate the short-term effects of partial left ventriculectomy (PLV) on left ventricular (LV) pressure-volume (P-V) loops, wall stress, and the synchrony of LV segmental volume motions in patients with dilated cardiomyopathy. BACKGROUND: Surgical LV volume reduction is under investigation as an alternative for, or bridge to, heart transplantation for patients with end-stage dilated cardiomyopathy. METHODS: We measured P-V loops in eight patients with dilated cardiomyopathy before, during and two to five days after PLV. The conductance catheter technique was used to measure LV volume instantaneously. RESULTS: The PLV reduced end-diastolic volume (EDV) acutely from 141+/-27 to 68+/-16 ml/m2 (p < 0.001) and to 65+/-6 ml/m2 (p < 0.001) at two to five days postoperation (post-op). Cardiac index (CI) increased from 1.5+/-0.5 to 2.6+/-0.6 l/min/m2 (p < 0.002) and was 1.8+/-0.3 l/min/m2 (NS) at two to five days post-op. The LV ejection fraction (EF) increased from 15+/-8% to 35+/-6% (p < 0.001) and to 26+/-3% (p < 0.003) at two to five days post-op. Tau decreased from 54+/-8 to 38+/-6 ms (p < 0.05) and was 38+/-5 ms (NS) at two to five days post-op. Peak wall stress decreased from 254+/-85 to 157+/-49 mm Hg (p < 0.001) and to 184+/-40 mm Hg (p < 0.003) two to five days post-op. The synchrony of LV segmental volume changes increased from 68+/-6% before PLV to 80+/-7% after surgery (p < 0.01) and was 73+/-4% (NS) at two to five days post-op. The LV synchrony index and CI showed a significant (p < 0.0001) correlation. CONCLUSIONS: The acute decrease in LV volume in heart-failure patients following PLV resulted at short-term in unchanged SV, increases in LVEF, and decreases in peak wall stress. The increase in LV synchrony with PLV suggests that the transition to a more uniform LV contraction and relaxation pattern might be a rationale of the working mechanism of PLV.

Myocardial enzyme depletion in infarcted human hearts: infarct size and equivalent tissue mass.

Myocardial activities of several enzymes were measured in infarcted and non-infarcted areas of heart sections obtained from eight patients who died after acute myocardial infarction. Similar data were obtained from four patients with cardiovascular disorders who died from causes other than myocardial infarction and from six patients without previously known heart disease. It was found that both non-infarcted and infarcted tissue samples contained considerably altered enzyme activities. This finding explains the low correlations between enzymatic and histological estimates of infarct size previously reported. However, when the residual myocardial activities of different enzymes were compared with each other, a close correlation was found between creatine kinase, alpha-hydroxybutyrate dehydrogenase, and aspartate aminotransferase. It appears that the pathological changes in the myocardial activities of these enzymes may be explained by the phenomenon of diluted myocardium. This indicates that myocardial injury, as estimated from plasma enzyme activities, may still be expressed meaningfully in gram equivalents of healthy myocardium.

Imipramine induced heart failure in the dog: a model to study the effect of cardiac assist devices.

OBJECTIVE: The value of intravenous imipramine in creating a reversible model of short term heart failure was evaluated in anaesthetised dogs. METHODS: Acute effects of imipramine were studied in 11 dogs using invasive haemodynamic pressure measurements and two dimensional echo evaluation. RESULTS: After a 30 min imipramine infusion (7.5 mg.kg-1.h-1), positive left ventricular dP/dtmax decreased from 1368(SEM 108) to 909(119) mm Hg.s-1 (p < 0.05), left ventricular end diastolic pressure increased from 8(1) to 12(2) mm Hg (p < 0.05), while left ventricular pressure decreased from 106(4) to 87(6) mm Hg (p < 0.05). Cessation of imipramine administration resulted within 60 min in partial restoration of cardiac function. This deterioration and subsequent recovery was also demonstrated with echocardiographic measurements, which showed a decrease in ejection fraction from 54(3)% to 28(2)% (p < 0.05). During administration of imipramine neither significant electrophysiological changes nor supraventricular/ventricular arrhythmias were seen. Repeated infusions of imipramine in three anaesthetised dogs with a two week interval showed the reproducibility of the haemodynamic effects and the recovery of ventricular function. Since the model was developed to evaluate the use of cardiomyoplasty in heart failure, the effect of imipramine was also evaluated on latissimus dorsi muscle contraction. Administration of imipramine did not affect skeletal muscle force development at the dosage used to create heart failure. CONCLUSIONS: This model can be used to produce short term reversible heart failure in anaesthetised animals to test the efficacy of supportive interventions like dynamic cardiomyoplasty, intra-aortic balloon pumping, and mechanical cardiac assist devices.

Metabolic and haemodynamic changes in the heart during the early phase of cardiopulmonary bypass: I. Clinical observations.

Knowledge of the effects of cardiopulmonary bypass on the myocardium and on cardiac function is limited. We therefore studied changes in haemodynamics and myocardial metabolism during the initial phase of cardiopulmonary bypass in two patient groups. In one group "normothermia" (34 degrees C) was used while on bypass, with an empty beating heart; in the other group hypothermia (range 27-33 degrees C) with ventricular fibrillation was used. Mean aortic pressure and myocardial oxygen consumption decreased significantly in both groups after instalment of CPB. The arterial-coronary sinus differences in lactate changed to negative values within 5 min of the start of bypass, indicating release instead of uptake of lactate. This release was maintained during the observation period and increased significantly in the hypothermic patient group when the ventricles were fibrillating. Therefore in patients undergoing aorto-coronary bypass surgery, detrimental changes in the myocardium must be anticipated during the initial phase of cardiopulmonary bypass prior to aortic cross clamping.

Metabolic and haemodynamic changes in the heart during the early phase of cardiopulmonary bypass: II. Animal experiments.

A significant release of lactate instead of uptake was observed during the first 10 min of cardiopulmonary bypass preceding aorto-coronary bypass surgery in human patients. To clarify these findings in more detail, myocardial lactate and oxygen metabolism was studied in healthy dog hearts subjected to a protocol similar to the clinical situation. In one group (n = 11) normothermia at 34 degrees C was used with an empty beating heart, and in the other group (n = 11) hypothermia with ventricular fibrillation was applied. Within the first 10 min of bypass no significant changes in high energy phosphates were observed in myocardial biopsies. However, a marked decrease in mean aortic blood pressure and a simultaneous lowering in oxygen consumption was observed in both groups after instalment of bypass. An initial shift from lactate uptake to lactate release occurred while on bypass in the normothermia group. After 10 min of bypass, lactate uptake was restored in hearts of both groups. Therefore, the lactate release during the initial phase of bypass in patients originates both from the instalment of the bypass and from (local) inadequate perfusion, which is most likely to be due to stenosed coronary arteries.

Changes in myocardial high-energy phosphate stores and carbohydrate metabolism during intermittent aortic crossclamping in dogs on cardiopulmonary bypass at 34 degrees and 25 degrees C.

The effect of cooling to 25 degrees C on myocardial metabolism was studied during four periods of global ischemia (10 minutes each) followed by 15 minutes of reperfusion in dogs on cardiopulmonary bypass. Systemic and heart temperature at normothermia (group N, 34 degrees C; n = 15) was compared with general hypothermia (group H, 25 degrees C; n = 16). Before and at the end of each aortic crossclamp period in small myocardial biopsy specimens the adenosine triphosphate, creatine phosphate, inorganic phosphate, glycogen, and lactate content was analyzed. Also, lactate and inorganic phosphate were measured in the coronary effluents during the repetitive periods of reperfusion. Hemodynamic function was not different at 60 minutes after cardiopulmonary bypass compared with pre-cardiopulmonary bypass values, and was not different between the groups N and H. The tissue content of adenosine triphosphate and glycogen decreased progressively during the experimental period, resulting in slightly depressed values in both groups at the end of cardiopulmonary bypass. Pronounced effects of ischemia and reperfusion on tissue content of creatine phosphate, inorganic phosphate, and lactate were observed after each period of ischemia. The net decrease in tissue creatine phosphate content was not different between groups N and H (41 +/- 4 versus 38 +/- 4 mumol.gm-1 dry weight; mean +/- standard error of the mean) after 10 minutes of ischemia. However, during ischemia the net inorganic phosphate increase in myocardial tissue was significantly higher in group H (70 +/- 7 mumol.gm-1) than in group N (44 +/- 3 mumol.gm-1). These findings do not support the notion that myocardial protection is improved during hypothermia. Moreover, quantitatively the release of inorganic phosphate and lactate did not correlate with the amount accumulated in the myocardial tissue during the preceding periods of ischemia. The release appeared to be temperature dependent, that is, significantly reduced at 25 degrees C. The present data demonstrate why clinical outcome is satisfactory in both surgical procedures, when in general the periods of aortic crossclamping do not exceed 10 minutes each and the reperfusion periods in between the ischemic episodes last about 15 minutes. Besides, the findings indicate that hypothermia is not strictly necessary under these circumstances.

Epicardial left ventricular lead placement for cardiac resynchronization therapy: optimal pace site selection with pressure-volume loops.

OBJECTIVES: Patients in heart failure with left bundle branch block benefit from cardiac resynchronization therapy. Usually the left ventricular pacing lead is placed by coronary sinus catheterization; however, this procedure is not always successful, and patients may be referred for surgical epicardial lead placement. The objective of this study was to develop a method to guide epicardial lead placement in cardiac resynchronization therapy. METHODS: Eleven patients in heart failure who were eligible for cardiac resynchronization therapy were referred for surgery because of failed coronary sinus left ventricular lead implantation. Minithoracotomy or thoracoscopy was performed, and a temporary epicardial electrode was used for biventricular pacing at various sites on the left ventricle. Pressure-volume loops with the conductance catheter were used to select the best site for each individual patient. RESULTS: Relative to the baseline situation, biventricular pacing with an optimal left ventricular lead position significantly increased stroke volume (+39%, P =.01), maximal left ventricular pressure derivative (+20%, P =.02), ejection fraction (+30%, P =.007), and stroke work (+66%, P =.006) and reduced end-systolic volume (-6%, P =.04). In contrast, biventricular pacing at a suboptimal site did not significantly change left ventricular function and even worsened it in some cases. CONCLUSIONS: To optimize cardiac resynchronization therapy with epicardial leads, mapping to determine the best pace site is a prerequisite. Pressure-volume loops offer real-time guidance for targeting epicardial lead placement during minimal invasive surgery.

In vivo tissue compatibility of two radio-opaque polymeric biomaterials.

Polymeric biomaterials featuring intrinsic radio-opacity continue to attract considerable scientific attention. This work focusses on two polymers that contain covalently bound iodine, rendering the materials radio-opaque. The first material is hard, transparent and glass-like, and consists of methyl methacrylate, 2-(2'-iodobenzoyl)-ethyl methacrylate (1) and 2-hydroxyethyl methacrylate (HEMA), in the molar ratio 65:20:15, respectively. The second material is a cross-linked hydrophilic network, consisting of HEMA and 1, in the molar ratio 80:20, respectively. Both materials were characterized by means of different physico-chemical techniques, including magic-angle-spinning solid state NMR spectroscopy, infrared spectroscopy and differential scanning calorimetry. Moreover, both materials were implanted subcutaneously in rats for 24 days. Upon explanation and histological examination, it appeared that both materials were well tolerated. No tissue necrosis, abscess formation or inflammation were observed. The samples were found to be surrounded by a vascularized capsule consisting of connective tissue cells. The results reveal excellent tissue compatibility for both materials. This is an important observation, since tissue compatibility is absolutely necessary for the applications which are foreseen for this type of radio-opaque biomaterials.

Studies on a new radiopaque polymeric biomaterial.

A new radiopaque polymeric biomaterial has been synthesized. The material, which actually represents an entire family of analogous radiopaque materials, is composed of 2-(p-iodobenzoyl)-ethyl methacrylate (compound 1, 21 mol%), methyl methacrylate (MMA, 60 mol%), and 2-hydroxyethyl methacrylate (HEMA, 19 mol%). The terpolymer was synthesized in a radical polymerization reaction at elevated temperature in N,N-dimethylformamide (DMF). The product was subjected to a set of physicochemical characterization techniques (gel permeation chromatography, 500 MHz 1H NMR in deuterated dimethylsulphoxide (d6-DMSO) solution, differential scanning calorimetry, dynamic water contact angle measurements), as well as to an in vitro thrombogenicity assay. Furthermore, scanning electron microscopy was used to study interactions of the material with blood platelets. The most important findings are: (a) the material is a genuine polymer with excellent X-ray visibility, even in the form of thin (0.4 mm) drawn fibres. This was established under realistic conditions. (b) The material exhibits low in vitro thrombogenicity, i.e. comparable to polyvinyl chloride, which is known as a passive material. These observations lead us to the suggestion that this type of radiopaque polymer holds promise with respect to application as a construction material for a new type of endovascular stent. This could be relevant in particular to stents to be used in conjunction with percutaneous transluminal coronary angioplasty (PTCA), also known as Dottering. Currently there is a clear trend away from metallic stents towards all-polymeric stents, since the latter have superior biocompatibility.(ABSTRACT TRUNCATED AT 250 WORDS)

Differences in metabolic response of dog and goat latissimus dorsi muscle to chronic stimulation.

The latissimus dorsi (LD) muscle is considered suitable to assist ventricular mechanical function in either cardiomyoplasty or extra-aortic-assist devices. Such application requires that this mixed-type skeletal muscle be transformed into a fatigue-resistant muscle, the adaptation of which can be elicited by chronic stimulation. In this study the LD muscles of dog and goat were subjected in situ to 12 wk of continuous electrical stimulation through intramuscular electrodes, and their myofibrillar and metabolic adaptations were compared. A gradual increase in the contraction rate of the muscle (in 10 wk from 30 to 80 contractions/min) caused the proportion of immunohistochemically identified type I fibers to increase in dog muscle from 30 to 74% and in goat muscle from 21 to 99%. Correspondingly, the anaerobic-glycolytic activity (fructose-6-phosphate kinase and lactate dehydrogenase activities) decreased by approximately 75% in both dog and goat muscles, whereas the oxidative capacity (fatty acid oxidation and citrate synthase activity) increased two- to threefold in goat LD muscle but remained unaltered in dog LD muscle. Muscular contents of high-energy phosphates and endogenous substrates were maintained, but the L-carnitine content decreased by 43% in both dog and goat. Our data further indicate that, for the monitoring of the metabolic adaptation of skeletal muscle, the ratio of activities of the oxidative and anaerobic-glycolytic pathways (e.g., citrate synthase to fructose-6-phosphate kinase activities) is a useful parameter in both dog and goat.(ABSTRACT TRUNCATED AT 250 WORDS)

L-carnitine combined with minimal electrical stimulation promotes type transformation of canine latissimus dorsi.

In the first part of this study, in four dogs the left latissimus dorsi was equipped to perform in vivo contraction measurements and the right latissimus dorsi served as control. After a control period, the dogs received L-carnitine intravenously for 8 wk. We found that carnitine caused the percentage of type I fibers to increase from 30 to 55% in the left latissimus dorsi but no change in the right latissimus dorsi. In the left latissimus dorsi, the contraction speed (percentage ripple) decreased from 75 to 30% and cytochrome-c oxidase activity increased 1.6-fold. No changes occurred in the right latissimus dorsi. To verify these observations, we performed a second study with placebo control for 8 wk, and only the left latissimus dorsi was subjected to weekly electrical stimulation. In the carnitine-treated dogs, the stimulated muscle showed an increase in the percentage of type I fibers from 16 to 35% and the ripple decreased from 92 to 77%. These measures did not change in the placebo-treated dogs. We concluded that weekly short-term stimulation does not lead to a change in fiber type; however, carnitine combined with minimal stimulation of the muscle leads to a significant shift in muscle fiber type composition toward a muscle with an increased content of type I fibers.

Changes in canine latissimus dorsi muscle during 24 wk of continuous electrical stimulation.

To study functional, structural, and biochemical adaptations to electrical stimulation of striated muscle in a large animal, the canine latissimus dorsi (LD) muscle was conditioned continuously for 24 wk with an increasing number of pulse bursts (burst duration 250 ms, burst frequency 30 Hz). Force measurements in vivo after 12 wk showed a significant decrease in the ripple, the ratio of interstimulus to peak force amplitude, from 0.94 +/- 0.03 to 0.13 +/- 0.08 (SE; n = 8, P less than 0.05), indicating reduction in contractile speed. Also the steep part of the force-frequency relation shifted to lower frequencies. A significant change in fiber-type composition was seen with both enzyme- and immunohistochemistry, manifested by an increase of type I fibers from 29.5 +/- 2.9 to 83 +/- 8% (SE; n = 8, P less than 0.05). During this period a transient rise in the number of type IIc/Ic fibers (from 3 to 10%) was seen. In the stimulated muscle, capillary-to-fiber ratio increased from 1.9 +/- 0.4 to 2.7 +/- 0.1 (P less than 0.05). A significant increase in mitochondrial volume was also seen, especially in the peripheral part of the fiber. Both creatine kinase and lactate dehydrogenase revealed a significant decline in activity within 12 wk. At the same time a shift in lactate dehydrogenase-isozyme pattern was observed toward the cardiac composition. No additional changes occurred after 12 wk of stimulation, indicating that conversion of the canine LD muscle was complete within this period.

Three-dimensional electromechanical mapping: imaging in the operating room of the future.

BACKGROUND: Three-dimensional electromechanical mapping has previously been shown to be a clinically important tool for cardiac imaging and intervention. We hypothesized that this technology may be beneficial as an intraoperative modality for assessing cardiac hemodynamics and viability during cardiac surgery. We report here the use of this technology as an imaging modality for intraoperative cardiac surgery. METHODS: The tip of a locatable catheter connected to an endocardial mapping and navigating system is accurately localized while simultaneously recording local electrical and mechanical functions. Thus the three-dimensional geometry of the beating cardiac chamber is reconstructed in real time. The system was tested on 6 goats that underwent acute dynamic cardiomyoplasty and on 5 dogs that underwent left anterior descending (LAD) coronary artery ligation. RESULTS: The electromechanical mapping system provided an accurate three-dimensional reconstruction of the beating left ventricle during cardiomyoplasty. After the wrapping procedure, significant end-diastolic area reduction was noted in the base and mid parts of the heart (948 +/- 194 mm2 vs 1245 +/- 33 mm2, p = 0.021; and 779 +/- 200 mm2 vs 1011 +/- 80 mm2, p = 0.016). The area of the cross-section of the apex did not change during the operation. Acute infarcted tissue was characterized 3 days after LAD ligation by concomitant deterioration in both electrical and mechanical function. CONCLUSIONS: By providing both a clear view of the anatomical changes that occur during cardiac surgery, and an accurate assessment of tissue viability, electroanatomic mapping may serve as an important adjunct tool for imaging and analysis of the heart during cardiac surgery

The enabler right ventricular circulatory support system for beating heart coronary artery bypass graft surgery.

BACKGROUND: Beating heart coronary artery bypass graft surgery of the left anterior descending, diagonal, and right coronary artery can be performed safely with the Octopus Stabilization System. However, tilting of the heart, which is necessary to reach the obtuse marginal and distal right coronary arteries, causes hemodynamic instability. This study was performed to investigate the possible role of the Enabler right ventricular circulatory support system in counteracting this instability. METHODS: In 8 sheep, the Enabler cannula was introduced via the jugular vein and positioned with the inlet valve in the right atrium and outlet valve in the pulmonary artery. The Octopus was used to expose the inferior wall and the posterior wall of the left ventricle. The hemodynamic effects of this tilting with and without Enabler right ventricular support were recorded, including Pressure Volume (PV) loops measured by conductance catheters in both ventricles. RESULTS: Tilting caused a reduction in stroke volume (inferior 31%, posterior 17%) and Enabler activation increased stroke volume (inferior 13%, posterior 31%). CONCLUSIONS: Tilting the heart has severe hemodynamic consequences that can be partially counteracted by the use of the Enabler for right ventricle support.

Acute descending aortomyoplasty induces coronary blood flow augmentation.

BACKGROUND: Aortomyoplasty is a procedure aimed to improve cardiac output in patients suffering from heart failure. Stimulation of the latissimus dorsi muscle around the aorta produces hemodynamic effects similar to those of the intraaortic balloon pump. These may be maintained without the accompanying complications or the need for anticoagulation. The objective of this study was to test the acute effects of aortomyoplasty on coronary artery blood flow. METHODS: Eight mongrel dogs (18 to 30 kg) underwent acute descending aortomyoplasty. Several stimulation protocols were applied after wrapping of the latissimus dorsi muscle around the aorta in different surgical configurations. The left anterior descending coronary blood flow was measured using a transonic Doppler flow probe. Left ventricular and aortic pressures, proximal and distal to the aortomyoplasty site, were monitored continuously. RESULTS: Significant aortic diastolic pressure augmentation was expressed both as an increase in peak values, from 110 +/- 24 mm Hg to 120 +/- 24 mm Hg (p < 0.001) and as an increase in the diastolic integral, from 64 +/- 23 mm Hg x s to 84 +/- 37 mm Hg x s (p < 0.001). Concomitantly, peak left anterior descending coronary blood flow increased from 26 +/- 10 mL/min to 32 +/- 12 mL/min (p < 0.001). This was associated with an increase in the diastolic flow integral from 11 +/- 4 mL to 14 +/- 6 mL (p < 0.001). CONCLUSIONS: Descending aortomyoplasty induces significant augmentation of coronary blood flow. Optimal timing of muscle stimulation is important in achieving the best assist. This procedure may prove beneficial for end-stage ischemic patients.

The effect of diltiazem on myocardial recovery after regional ischemia in dogs.

The effect of diltiazem on post-ischemic metabolic and functional recovery was investigated in regionally ischemic dog hearts. The duration of ischemia was 60 min, followed by 60 min of reperfusion. Diltiazem (bolus injection of 0.1 mg X kg-1 body weight prior to ischemia, followed by a continuous infusion of 0.1 mg X kg-1 X h-1) had no effect on residual coronary flow in the centre of the ischemic area, but blunted the reactive hyperemia response after restoration of flow. The drug partially prevented the depletion of ATP and glycogen in the severely underperfused subendocardial layers, i.e. when residual flow was below 0.1 ml X min-1 X g-1. Reduction of the content of these substances in the subepicardial layers was moderate and not influenced by diltiazem. Segment shortening in the subepicardial layers disappeared whereas segment lengthening was observed in the subendocardial layers during the ischemic period. Diltiazem did not prevent the loss of contractile function. Despite an initial restoration of contractile function within 10 min after reperfusion, no significant beneficial effect of diltiazem treatment on mechanical function of the reperfused area was present thereafter.

Cardiomyoplasty as an isolated procedure to treat refractory heart failure.

OBJECTIVE: Cardiomyoplasty represents a controversial therapy for chronic heart failure. The aim of this study is to review our experience of such a surgical procedure as an isolate approach to treat refractory left ventricular dysfunction. METHODS: Twenty-two patients were considered candidates for cardiomyoplasty because of chronic heart failure. Mean age was 58.7 +/- 5.3 (range 48-71 years), 19 patients were male and 3 were female. Ischemic or idiopathic etiology was present in 11 cases, respectively. Traditional as well as innovative techniques were used to assess hemodynamic function. Pre-operative hemodynamic profile included mean left ventricular ejection fraction of 20 +/- 5.8% (9-28%), absence of severe right ventricular failure, and mean left ventricular end-diastolic diameter of 75.5 +/- 7.4 mm (range 61-92 m). All patients were in New York Heart Association Class III or Intermittent IV despite conventional medical therapy. RESULTS: There was no intra-operative death. No additional surgery was performed. Left latissimus dorsi (LD) muscle was used in 20 cases, and right LD in two patients. Early mortality occurred in one patient (low cardiac output syndrome), whereas late mortality in five patients (three sudden deaths, one lung cancer, one heart failure). Mean follow-up is 20.7 +/- 16.7 months (3-51 months). Actuarial survival at 4 years is 70%. Cardiac index increased at 6 months (3.08 +/- 0.5 l/min per m2, P = 0.04), but no other significant changes were observed in the long term (3.03 +/- 0.7 l/min per m2, 3 +/- 0.7 l/min per m2, and 2.85 +/- 0.7 l/min per m2, at 12, 24 and 36 months, respectively). Ejection fraction improved at 6 and 12 months (29.1 +/- 1.03%, P = 0.0017; and 27.3 +/- 5.6%, P = 0.0091, respectively), while no substantial augmentation was documented at 2 and 3 years (25.6 +/- 2.5% and 25.1 +/- 4.0%, respectively). Left ventricular end-diastolic diameter was markedly reduced at 6 (73.2 +/- 8.0 mm, P = 0.0176), 12 (69.4 +/- 8.5 mm, P = 0.002) and 24 months (71.1 +/- 7.0 mm, P = 0.011), and was then stable (74.0 +/- 9.1 mm, P = 0.47) at 36 months. Postoperative pressure/volume loop evaluation showed some improvement of hemodynamic function from skeletal muscle assistance. Acute pulmonary edema episodes, as well as number of hospitalizations, were considerably reduced following cardiomyoplasty. CONCLUSIONS: In our experience, cardiomyoplasty was shown to exert moderate beneficial influence on left ventricular performance, to significantly reduce cardiac dilatation and to promote the stabilization of the disease course.