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[Regional assessment of treatment in lung cancer using lung perfusion and ventilation images].

In 30 patients with lung cancer undergoing non-surgical treatment, we performed perfusion lung imaging using 99mTc-MAA and inhalation lung studies using Technegas before and after treatment and evaluated regional perfusion and ventilation status in the lung regions where bronchogenic carcinoma was located. Regional ventilation status was preserved rather than perfusion counterpart (V > P) in 18 patients (18/30 = 60.0%) before treatment, while the former was better than the latter in 27 patients (27/30 = 90.0%) after treatment, indicating that regional ventilation status improved more significantly than regional perfusion counterpart after treatment (p = 0.005). We also classified the therapeutic effect for regional perfusion and ventilation status as improved, unchanged, or worsened, respectively; improvement in regional perfusion status was observed in 17 patients (56.7%) and that in regional ventilation status in 24 patients (80.0%). There was a statistically significant correlation between improved regional perfusion and ventilation status (p = 0.0018) when therapeutic effect was recognized. The patients who showed improvement in regional perfusion status after treatment always showed improved regional ventilation status, but 7 patients showed either unchanged or worsened regional perfusion status after treatment, although regional ventilation status was improved. In conclusion the pulmonary vascular beds seem more vulnerable to bronchogenic carcinoma and improvement in regional perfusion status was revealed to be more difficult than that in regional ventilation status after treatment.

Adult↗

[Bacterial growth in the perfusion medium of the isolated rat brain and its inhibition by antibiotics].

In the perfusion medium of the isolated rat brain the bacterial content was examined. The perfusion medium used contained 30% bovine erythrocytes, 2 g% bovine serum albumin and about 13 mM glucose in Krebs-Henseleit-solution. Before the perfusion of the isolated rat brain was started the medium recirculated up to two hours in the perfusion apparatus. After this, the perfusion of the isolated rat brain was carried out for four hours. At various times and at different points of the circulating system samples of the perfusion medium were withdrawn and tested for their bacterial content. Using the plate count procedure, at the end of the perfusion 10(5) to 10(6) bacteria per ml medium were found. This order of magnitude of the bacterial content suggested that it is not necessary to add antibacterial substances to the medium when perfusions lasted up to 4 hours. Nevertheless, from each sample 10 bacteria species were isolated and their sensitivity against 15 different antibacterial substances was tested. The substances were ampicillin, carbenicillin, cephaloridine, chloramphenicol, cloxacillin, erythromycin, gentamycin, nalidixic acid, neomycin, nitrofurantoin, penicillin, polymyxin B, sulfadiazine, tetracycline and trimethoprim + sulfamethoxazole. Tetracycline was most active in inhibiting bacterial growth. 1 mg and 0.5 mg tetracycline added to 100 ml perfusion medium were able to prevent an increase of the bacterial count during the perfusion experiments.

Animals↗

Intraoperative chemohyperthermic peritoneal perfusion as an adjuvant to gastric cancer: final results of a randomized controlled study.

BACKGROUND/AIMS: Although the most frequent cause of death after curative resection of advanced gastric cancer is peritoneal recurrence, there was no effective therapy for the prevention of peritoneal recurrence. This randomized trial sought to determine whether intraoperative chemohyperthermic peritoneal perfusion could eliminate microscopic residual disease and thereby improve survival of patients with advanced gastric cancer. METHODOLOGY: One-hundred and thirty-nine patients with T2-4 gastric cancer underwent curative gastrectomy with extended lymphadenectomy. These patients were randomly allocated into the following three groups. Patients in the CHPP group received surgery + chemohyperthermic peritoneal perfusion, and those in the CNPP group underwent surgery + chemonormothermic peritoneal perfusion. The third group was surgery alone group. In the CHPP and CNPP groups, peritoneal cavity was perfused with 6-8 liters of heated saline at, respectively, 42-43 degrees C and 37 degrees C with 30 mg of mitomycin C and 300 mg of cisplatin by a extracorporeal circulation machine. RESULTS: Major operative complication occurred in 19% (9/48), 14% (6/44) and 19% (9/47) of the CHPP, CNPP and surgery alone group, respectively. Complication which uniquely developed after chemohyperthermic peritoneal perfusion was bowel perforation. Mortality rates of each group were 4% (2/48), 0% (0/44) and 4% (2/47) in the CHPP, CNPP and surgery alone group, respectively. Overall 5-year survival rates of CHPP, CNPP and surgery alone groups were 61%, 43% and 42%, respectively. In a subset analysis, patients with gastric cancer having serosal invasion or lymph node metastasis have shown a statistically significant improvement in survival when treated with chemohyperthermic peritoneal perfusion. However, chemonormothermic peritoneal perfusion had no survival benefit. By analyzing with Cox proportional hazard model, chemohyperthermic peritoneal perfusion emerged as an independent prognostic factor for good survival. Surgery alone had three-fold higher risk of death than chemohyperthermic peritoneal perfusion. CONCLUSIONS: Chemohyperthermic peritoneal perfusion had an efficiency for the prophylaxis of recurrence after curative resection of advanced gastric cancer, and is indicated for patients with tumor infiltrating beyond serosal layer and node positive tumor.

Chemotherapy, Adjuvant↗

Mechanical assistance of the left ventricle: acute effect on cardiac performance and coronary flow of different perfusion patterns.

Mechanical circulatory assistance by ventricular assist devices provides an opportunity to influence the aortic pressure pattern, which may affect ventricular loading and coronary perfusion. The effect of synchronous, pulsatile coronary perfusion of an assist device-supported left ventricle has not been studied. To analyze the effect of different perfusion patterns on left ventricular performance and on coronary flow, independent of pressure and volume loading, we used three different modes of aortic perfusion in an isometric, contracting, isolated canine heart model. The effect of nonpulsatile, counter-pulsatile, and copulsatile coronary perfusion was analyzed in four subgroups to simulate different, clinically relevant situations (using two different ventricular end-diastolic volumes [normal and high] and two mean perfusion pressures [normal and critically low]). Our experiments demonstrated that total coronary flow is optimized by making the perfusion pressure pulsatile and by synchronously timing the pump systole with ventricular diastole (counterpulsation). Under identical conditions of preload and mean perfusion pressure, coronary flow and left ventricular contractility were decreased during non-pulsatile and copulsatile aortic perfusion when compared with counterpulsatile flow. There were no significant differences between the nonpulsatile and copulsatile modes. We conclude from these data that a nonejecting, but contracting, left ventricle will have improved systolic function and coronary blood flow if the coronary perfusion pressure is synchronized in a counterpulsatile manner. This is a significant implication for mechanical left ventricular assist devices when used to promote myocardial recovery.

Animals↗

Selective visceral perfusion during thoracoabdominal aortic aneurysm repair.

PURPOSE: To evaluate the effectiveness of selective visceral perfusion during repair of an thoracoabdominal aortic aneurysm (TAAA), we compared the postoperative renal and hepatic functions (blood urea nitrogen, serum creatinine, total bilirubin, glutamate pyruvate transaminase) between the two groups with and without perfusion. PATIENTS AND METHODS: We operated on 52 patients with TAAA. Among them, the visceral vessels were reconstructed in 22 patients with selective visceral perfusion and in 12 patients without perfusion. The average selective perfusion time was 49.5+/-25.5 min. in the celiac and superior mesenteric arteries and 32.8+/-18.8 min. in the renal arteries. The average perfusion flow rate per each visceral vessel was 155.4+/-97.4 ml/min. RESULTS: There were five hospital deaths. There was no significant difference between the groups in the postoperative value of four factors. The selective perfusion time for vessel reconstruction in the selective visceral perfusion group was significantly longer than the arterial clamp time for vessel reconstruction in the non-perfusion group (49.5+/-25.5 min. vs. 25.6+/-13.4 min.). CONCLUSION: Our selective visceral perfusion method is not only beneficial for organ protection, but also provides us with the necessary time to reimplant the visceral as well as intercostal or lumbar arteries.

Adult↗

Effect of enhanced red blood cell aggregation on blood flow resistance in an isolated-perfused guinea pig heart preparation.

The role of red blood cell (RBC) aggregation as a determinant of in vivo blood flow is still unclear. This study was designed to investigate the influence of a well-controlled enhancement of RBC aggregation on blood flow resistance in an isolated-perfused heart preparation. Guinea pig hearts were perfused through a catheter inserted into the root of the aorta using a pressure servo-controlled pump system that maintained perfusion pressures of 30 to 100 mmHg. The hearts were beating at their intrinsic rates and pumping against the perfusion pressure. RBC aggregation was increased by Pluronic (F98) coating of RBC at a concentration 0.025 mg/ml, corresponding to about a 100% increment in RBC aggregation as measured by erythrocyte sedimentation rate. Isolated heart preparations were perfused with 0.40 l/l hematocrit unmodified guinea pig blood and with Pluronic-coated RBC suspensions in autologous plasma. At high perfusion pressures there were no significant differences between the flow resistance values for the two perfusates, with differences in flow resistance only becoming significant at lower perfusion pressures. These results can be interpreted to reflect the shear dependence of RBC aggregation: higher shear forces associated with higher perfusion pressures should have dispersed RBC aggregates resulting in blood flow resistances similar to control values. Experiments repeated in preparations in which the smooth muscle tone was inhibited by pre-treatment with papaverine indicated that significant effects of enhanced RBC aggregation could be detected at higher perfusion pressures, underlining the compensatory role of vasomotor control mechanisms.

Adaptation, Physiological↗

Uniform tissues engineered by seeding and culturing cells in 3D scaffolds under perfusion at defined oxygen tensions.

In this work, we assessed whether culture of uniformly seeded chondrocytes under direct perfusion, which supplies the cells with normoxic oxygen levels, can maintain a uniform distribution of viable cells throughout porous scaffolds several milimeters in thickness, and support the development of uniform tissue grafts. An integrated bioreactor system was first developed to streamline the steps of perfusion cell seeding of porous scaffolds and perfusion culture of the cell-seeded scaffolds. Oxygen tensions in perfused constructs were monitored by in-line oxygen sensors incorporated at the construct inlet and outlet. Adult human articular chondrocytes were perfusion-seeded into 4.5 mm thick foam scaffolds at a rate of 1 mm/s. Cell-seeded foams were then either cultured statically in dishes or further cultured under perfusion at a rate of 100 microm/s for 2 weeks. Following perfusion seeding, viable cells were uniformly distributed throughout the foams. Constructs subsequently cultured statically were highly heterogeneous, with cells and matrix concentrated at the construct periphery. In contrast, constructs cultured under perfusion were highly homogeneous, with uniform distributions of cells and matrix. Oxygen tensions of the perfused medium were maintained near normoxic levels (inlet congruent with 20%, outlet > 15%) at all times of culture. We have demonstrated that perfusion culture of cells seeded uniformly within porous scaffolds, at a flow rate maintaining a homogeneous oxygen supply, supports the development of uniform engineering tissue grafts of clinically relevant thicknesses.

Adult↗

Activated neutrophils injure the isolated, perfused rat liver by an oxygen radical-dependent mechanism.

Under certain circumstances, segmented neutrophils (PMNs) injure extrahepatic tissue by releasing toxic oxygen species and degradative enzymes. The authors used an isolated, perfused rat liver preparation to determine whether PMNs might injure the liver. Livers from fasted rats were perfused with Krebs-Ringer bicarbonate buffer (pH 7.4) containing 3% bovine serum albumin (BSA) in a recirculating system. Rat peritoneal PMNs (4 x 10(8] or vehicle (Hank's balanced salt solution [HBSS], pH 7.35) were added, and liver injury was assessed 90 minutes later by release of alanine aminotransferase (ALT) into the perfusion medium and histopathologic analysis of liver sections. Perfusion of livers receiving only HBSS for 90 minutes resulted in a small increase in ALT activity in the perfusion medium but did not significantly alter histologic features of liver sections. Addition of unstimulated PMNs did not increase further the ALT activity and, with the exception of vascular neutrophilia, did not significantly change the histomorphology compared with controls. When PMNs activated with a combination of phorbol myristate acetate (PMA, 31 ng/ml) and lithocholate (100 mumol/l [micromolar]) were added to the perfusion system, however, livers released greater amounts of ALT than those perfused with PMA, lithocholate, and HBSS. Activated PMNs caused a transient reduction in flow of perfusion medium that lasted approximately 5 to 15 minutes. Liver sections had multifocal to coalescing foci of moderate to severe, acute hepatocellular necrosis associated with the areas of intense sinusoidal neutrophilia. In addition a second type of lesion was observed and was characterized by triangular foci of necrosis located adjacent to periportal regions of sinusoids or portal veins containing neutrophilic thrombi. These lesions were void of PMNs and were consistent with infarcts. A combination of superoxide dismutase and catalase added to the perfusion medium (500 U/ml each) prevented the elevation in ALT activity but not the transient reduction in flow. These results indicate that activated PMNs may cause liver injury by an oxygen radical-dependent mechanism. It is unclear whether PMN-derived oxygen radicals, hepatocellular-derived oxygen species resulting from reduced tissue perfusion and reperfusion, or both are involved in the pathogenesis.

Alanine Transaminase↗

Improved immediate function of renal allografts with Belzer perfusate.

The characteristics of 254 cadaveric kidneys were evaluated and the incidence of immediate function identified. The Belzer perfusate was used primarily (n = 140) and secondarily (n = 14) in combination with pulsatile machine perfusion. These two groups were compared with a previous group of kidneys machine-perfused with silica gel (cryoprecipitated human plasma). The incidence of immediate function of the group primarily perfused with Belzer perfusate was statistically significantly improved over that of the silica gel. The secondarily perfused Belzer group, "imported" kidneys previously preserved with simple cold storage, had notably longer periods of preservation and higher resistances on the machine. However, 100% of this group functioned immediately. Other findings in this study show that the Belzer perfusate allows for improved parenchymal function posttransplant, as noted by a more rapid clearance of serum creatinine posttransplant. When comparing the immediate function group with those suffering early dysfunction, there is a statistically significant increased resistance on the machine in the latter group. This allows for prediction of immediate function based on perfusion characteristics of the kidney. The Belzer perfusate, composed of metabolic substrates for high-energy phosphate production, improves the incidence of immediate function in machine-perfused kidneys, as well as improved qualitative function posttransplant. It also is effective as a "rescue" mechanism in previously simple cold-stored (ATP-depleted) kidneys.

Adenosine Triphosphate↗

[Selective continuous coronary perfusion via an angioplasty catheter following acute vascular occlusion].

Since surgical revascularisation after PTCA-induced acute coronary occlusion in the majority of cases is delayed by at least 2 hours, we assessed the possibility of selective, volume-controlled coronary perfusion via the still indwelling angioplasty catheter for such a prolonged period using an external pump. Because of the high pressures required to provide adequate flow through many of the currently used catheters, an AC independent, pressure and volume controlled pump was developed which does not cause substantial hemolysis even at pressures beyond 10 atm. During in vitro tests the pressure-flow-rate relations and the degree of hemolysis and blood count changes were determined for various catheters. The previous catheters with a fixed wire tip caused excessive hemolysis which rendered prolonged coronary perfusion prohibitive. But even with the more recent catheters the presence of side holes near the catheter tip may at times cause significant hemolysis. In 20 out of 22 dogs the anterior descending (n = 18) or circumflex (n = 2) coronary artery was selectively perfused for 2 hours following balloon occlusion. The perfusion rate was adjusted according to the occurrence of ischemic signs in the ECG and for a drop in the coronary venous oxygen saturation which was monitored with a fiberoptic catheter. The intraluminal pressure within the selectively perfused vessel was recorded continuously but not used for adjustment of the perfusion rate. In no case was there a critical pressure increase in the selectively perfused vessel. When perfusion of the occluded vessel was stopped after 2 hours, massive myocardial ischemia developed which was reversible with resumption of perfusion. Using an adequate pump and the more recent, steerable angioplasty catheters which should not have side holes near the tip, selective coronary perfusion can be performed for at least 2 hours and is capable of preventing myocardial ischemia.

Angioplasty, Balloon↗

[Effects of low-frequency pulsing magnetic field upon the respiratory metabolism and transmembrane ion fluxes of perfused rat livers].

UNLABELLED: Influence of magnetic fields on biological systems is not completely clear. Recently, experiments on the effects of weak not heat inducing electromagnetic fields concerning biological systems have been reported. We have investigated the effects of the weak low-frequency pulsing magnetic field (PMF) concerning the respiratory metabolism and transmembrane ion flux of perfused rat livers. MATERIALS AND METHODS: Livers from male Wistar rats were perfused via the portal vein with 95% O2-5% CO2 saturated Krebs-Henseleit Bicarbonate Buffer maintained at 32 degrees C. In 48 hrs fasted rats, lactate was administered in the perfusate as a substrate of gluconeogenesis in case of necessity. PMF generated by the solenoid coil was applied to the perfused livers. For monitoring of respiratory metabolism of the perfused livers, scanning spectrophotometry and NADH fluorometry were applied to the surface of the liver. The effluent was monitored for PO2 and analyzed for glucose, lactate and pyruvate. Ca2+, Mg2+, Na+, K+, Cl- ion from effluent were also analyzed. RESULTS: By being exposed to a low-frequency PMF, the O2 consumption increased in the perfused livers of the fed rats, but the degree was variable according to the metabolic state of the liver of each rat. In order to bring about a maximum reductive state, ethanol was given to the perfusate. Ethanol caused an increase in NADH and Lactate/Pyruvate ratio and O2 consumption and an inhibition of glucose production. By exposure to PMF the metabolism of perfused liver was shifted to the re-oxidative state. In lactate administered perfused liver of the 48 hrs fasted rats, PMF caused an increase in the livers sensitivity to glucagon. As regards the transmembrane ion fluxes, PMF acted antagonistically to the ethanol effect, especially when we used perfusate with low Ca2+ concentrations. So that an intimate association between PMF and intracellular Ca2+ regulating system was suggested.

Animals↗

An improved isolated working rabbit heart preparation using red cell enhanced perfusate.

The performance of isolated working rabbit hearts perfused with Krebs-Henseleit (KH) buffer was compared with those in which the buffer was supplemented with washed human red blood cells (KH + RBC) at a hematocrit of 15 percent. When perfused with KH alone at 70 cm H2O afterload and paced at 240 beats/minute, coronary flow was more than double, whereas aortic flow was 40-60 percent of that in hearts perfused with KH + RBC, regardless of left atrial filling pressures (LAFP). Peak systolic pressure reached a plateau at 120 mm Hg in KH + RBC, but at 95 mm Hg in the KH group. Stroke work, however, was similar in the two groups. Despite the high coronary flow, oxygen uptake by hearts perfused with KH was substantially less and did not respond to increases in LAFP as in those perfused with KH + RBC. There was a 20 percent drop in ATP and glycogen content after 90 minutes' perfusion. In contrast, isolated hearts perfused with RBC-enriched buffer remained stable for at least 150 minutes. Irrespective of the perfusate, triacylglycerol content of the muscle remained at similar levels throughout the course of study. Increasing RBC in the perfusate from 15 percent to 25 percent had no additional effect on cardiac performance or oxygen consumption. Our findings demonstrate that in the isolated working rabbit heart inclusion of RBC in the perfusate improves mechanical and metabolic stability by providing an adequate oxygen supply.

Animals↗

Perfusion characteristics and norepinephrine reactivity of human renal carcinoma.

Kidneys, surgically removed due to carcinoma, were subjected to perfusion in vitro. The perfusion distribution was studied by means of labeled microspheres injected during maximal vascular dilation and during two different norepinephrine concentrations. The perfusion concluded with injection of barium sulfate. Two-mm-thick slices of tissue were autoradiographed and microangiographed for visualization of perfusion and distribution of vascular density, respectively. Multiple specimens from tumor and cortical tissues were subjected to quantitative perfusate flow analysis. In spite of regionally high vascular density, perfusion through "normal-sized" capillaries was very low in tumor tissue as compared to cortex (during maximal dilation, one-tenth of the cortical flow). During moderate norepinephrine infusion, the perfusate flow decreased, and the resistance of the cortex increased. The flow to tumor tissue increased while the vascular resistance remained constant. During higher norepinephrine concentrations, the flow was redistributed; i.e., the cortical flow increased while that of the tumor decreased, due to a marked increase in tumor vascular resistance while the cortical tissue showed a very moderate rise in resistance. The thin-walled tumor vessels might be collapsed under a high tissue pressure at low perfusion pressures. At higher perfusion pressure, the vessels might open up, and contractile activity may not be expressed until then. The tumor vascular resistance increased 3 to 4 times, while that of cortex showed a 7-fold increase. Indications that a considerable fraction of the perfusate passes arteriovenous passages larger than 15 micron were obtained in individual experiments, this fraction increasing upon norepinephrine infusion.

Carcinoma↗

Caffeine-induced myocardial injury in calcium-free perfused rat hearts.

Hearts depleted of extracellular calcium become susceptible to injury caused by repletion of extracellular calcium (calcium paradox). It has been suggested that calcium-free perfusion causes weakening of intercalated disks and that the physical stress of contracture may cause sarcolemmal membrane rupture and creatine kinase (CK) release. To further investigate this hypothesis, the effects of caffeine on contracture, cellular morphology, and CK release were studied in control and calcium-free perfused isolated rat hearts. Control hearts perfused with 2.5 mM calcium retained normal ultrastructure for long periods of perfusion. Calcium-free hearts perfused for 12 minutes developed separations of fascia adherens portions of intercalated disks but retained intact nexus junctions. Hearts subjected to 5-minute calcium-free perfusion, followed by calcium repletion, developed a massive CK release and extensive contraction band necrosis (calcium paradox). Ten millimolar caffeine, which causes rapid calcium release from sarcoplasmic reticulum (SR), produced contracture, but not CK release, from control hearts perfused with medium containing 2.5 mM calcium. In calcium-free perfused hearts, caffeine caused sudden CK release accompanied by contracture, development of contraction bands, wide separations of cells at intercalated disks, and sarcolemmal membrane injury. Caffeine-induced injury occurred despite 3 mM amobarbital inhibition of mitochondrial respiration. Hearts perfused with caffeine in the presence of calcium relaxed when made calcium-free and did not release CK. Addition of caffeine following calcium-free perfusion at 22 C, which protects the heart from the calcium paradox, produced a rapid, transient contracture. These results are compatible with the hypothesis that myocardial cell injury in calcium-free hearts is not dependent on repletion of extracellular calcium or mitochondrial function, but can result from contracture following caffeine-induced release of intracellular calcium from the SR.

Amobarbital↗

Study of central regulation of intraocular pressure using ventriculocisternal perfusion.

The ability of hypoosmotic solution, prostaglandin E1 (PGE1) and clonidine to influence intraocular pressure (IOP) by a central mechanism was studied using the technique of ventriculocisternal perfusion in conscious rabbits. IOP remained unchanged during the perfusion of 150 mOsm artificial cerebrospinal fluid. IOP rapidly increased by 15 mmHg during the perfusion of PGE1 at the dose of 1 or 3 micrograms/min. However, when PGE1 was perfused intravenously at the dose of 1 microgram/min, a similar IOP response was observed. Furthermore, during the ventriculocisternal perfusion of PGE1 a significant systemic absorption occurred. These observations indicate that the ocular hypertension during the ventriculocisternal perfusion of PGE1 is primarily due to the peripheral action of systematically absorbed PGE1. IOP gradually decreased by 3 mmHg during the ventriculocisternal perfusion of clonidine at the dose of 0.1 or 0.33 micrograms/min. Intravenous perfusion of clonidine at the same doses did not change the IOP. These results indicate that clonidine can lower IOP by a centrally mediated mechanism. Ventriculocisternal perfusion of clonidine (0.1 micrograms/min) in rabbits with unilateral superior cervical ganglionectomy lowered IOP in both eyes, indicating that ocular adrenergic innervation does not participate in this centrally mediated IOP response. However, the cardiovascular parameters of anesthetized rabbits were altered by the ventriculocisternal perfusion of clonidine (0.1 micrograms/min), suggesting that a change in systemic hemodynamics is involved in the central IOP effect of clonidine.

Alprostadil↗

Correlative studies on sarcolemmal ultrastructure, permeability, and loss of intracellular enzymes in the isolated heart perfused with calcium-free medium.

Effects of calcium-free perfusion and calcium-free perfusion followed by reperfusion with calcium on sarcolemmal structure, sarcolemmal permeability, and creatine phosphokinase loss were investigated in isolated perfused rat hearts. Release of creatine phosphokinase was significant (P less than 0.0002) after 4-5 minutes of perfusion with Ca++-free medium, but later releases in comparison to their immediately preceding periods became significant only after more than 20-minute perfusion. Poor correlation between enzyme loss and lanthanum permeability prior to 20 minutes of Ca++-free perfusion was noted. After 20 minutes of Ca++-free perfusion, the basal lamina was separated from the plasma membrane, and lanthanum was seen in the cytoplasm. The intramembranous particles began to aggregate at that time. The morphologic and enzymatic changes were dramatic following reperfusion of calcium-free perfused hearts. Morphologic changes in these hearts included separation of basal lamina, cellular separation at the intercalated disk, dissolution of actin filaments at the region of I band, contraction bands, cell swelling, and staining or filling of mitochondrial membranes with La+++. Increased sarcolemmal permeability was associated with tears and aggregation of intramembranous particles in the sarcolemmal lipid bilayers. These results suggest that reperfusion of Ca++-free perfused cells causes irreversible damage to the sarcolemmal lipid bilayer, and the degree of alterations induced in the cells is dependent upon the initial duration of Ca++-free perfusion.

Animals↗

Effects of perfusion pressure on myocardial performance, metabolism, wall thickness, and compliance: comparison of the beating and fibrillating heart.

The effects of brief periods of graded reductions in perfusion pressure on normally beating and fibrillating hearts were examined. Mechanical and metabolic parameters were studied in the isolated, isovolumic (balloon in left ventricle), blood-perfused dog heart preparation. Experiments were carried out at perfusion pressures of 100, 75, 50, and 25 mm Hg, and comparisons of performance were made at the same ventricular volumes in the beating and fibrillating heart. A fall in perfusion pressure significantly decreased systolic performance in the beating heart. Diastolic pressure-volume relations were not altered by changes in perfusion pressure in the beating heart, but the fibrillating heart became significantly more compliant as perfusion pressure declined. Coronary blood flow and myocardial oxygen consumption were consistently higher during fibrillation than during sinus rhythm, and both parameters declined significantly at decreasing perfusion pressures. The fibrillating heart produced lactate at a perfusion pressure below 65 mm Hg, while the beating heart produced lactate at a perfusion pressure below 35 mm Hg. These studies demonstrate that brief periods of relatively modest decreases in perfusion pressure during ventricular fibrillation alter myocardial energy demand-supply relationships to result in ischemia of the fibrillating heart.

Animals↗

Effects of perfusion-induced edema on diastolic stress-strain relations in intact swine papillary muscle.

The mechanism through which edema reduces left ventricular compliance has not been defined. Accordingly, diastolic properties of in situ left ventricular swine papillary muscles were studied in three groups: control (n = 6, 4 degrees to 6 degrees C), edematous (150 mOsm/L coronary perfusion, n = 6, 4 degrees to 6 degrees C), and ischemic contracture (n = 8, 28 degrees C). Lagrangian stress (sigma) and strain (epsilon) were calculated from slow stretch data and approximated by sigma = alpha(e beta epsilon-1). The natural logarithm of stress versus strain was linear over the physiologic range of 0.05 < strain < 0.40. Hypotonic perfusions (1 L x 3) progressively shifted the stress-strain relationship upward and to the left. Compared to baseline, alpha increased significantly (p < 0.05) after perfusion 3 (6.7 +/- 2.1 baseline, 12.2 +/- 6.6 perfusion 1, 12.7 +/- 3.5 perfusion 2, and 42.9 +/- 16.3 gm/cm2 perfusion 3). The constant beta did not change significantly (13.0 +/- 1.5 baseline, 13.1 +/- 1.6 perfusion 1, 13.2 +/- 1.6 perfusion 2, and 14.1 +/- 1.4 perfusion 3). Right ventricular water content increased after each perfusion (77.1% +/- 1.4% baseline, 81.6% +/- 1.3%, 84.7% +/- 1.5%, and 86.9% +/- 1.7%, p < 0.05). With ischemic contracture, alpha increased from 61.9 +/- 17.8 to 173.1 +/- 61.5 gm/cm2 (p > 0.05) and beta increased insignificantly from 6.5 +/- 0.6 to 10.6 +/- 1.8 (p = NS). In the control group all variables were unchanged after 210 minutes. We conclude that myocardial stiffness increases with myocardial edema. This may explain decreased compliance in the edematous left ventricle.

Animals↗