Intermittent Perfusion Research Articles

Cerebral consequences of hypothermic circulatory arrest in adults.

Despite widespread use of hypothermic circulatory arrest (HCA) in aneurysm surgery and for repair of congenital heart defects, there is continued concern about possible adverse cerebral sequelae. The search for ways to improve implementation of HCA has inspired retrospective clinical studies to try to identify risk factors for cerebral injury, and clinical and laboratory investigations to explore the physiology of HCA. At present, risk factors associated with less favorable cerebral outcome after HCA include: prolonged duration of HCA (usually greater than 60 min); advanced patient age; rapid cooling (less than 20 min); hyperglycemia either before HCA or during reperfusion; preoperative cyanosis or lack of adequate hemodilution; evidence of increased oxygen extraction before HCA or during reperfusion; and delayed reappearance of electroencephalogram (EEG) or marked EEG abnormality. Strategies advocated to increase safety of HCA include: pretreatment with barbiturates and steroids; use of alpha-stat pH regulation during cooling and rewarming; intraoperative monitoring of EEG; slow and adequate cooling, including packing of the head in ice; monitoring of jugular venous oxygen content; hemodilution; and avoidance of hyperglycemia. Current investigation focuses on delineating the relationship of cerebral blood flow (CBF) to cerebral oxygen consumption and glucose metabolism during cooling, HCA, rewarming, and later recovery, and identifying changes in acute intraoperative parameters, including the presence of intracerebral enzymes in cerebral spinal fluid, with cerebral outcome as assessed by neurological evaluation, quantitative EEG, and postmortem histology. Clinically, intraoperative monitoring of EEG and measurement of CBF by tracer washout or Doppler flows are contributing to better understanding of the physiology of HCA, and in the laboratory, nuclear magnetic resonance (NMR) spectroscopy has provided valuable insights into the kinetics of intracerebral energy metabolism. Promising strategies for the future include investigation of other pharmacological agents to increase cerebral protection, and use of "cerebroplegia" or intermittent perfusion between intervals of HCA to improve cerebral tolerance for longer durations of HCA.

Cardiac protection during transplantation: Intermittent versus continuous cardioplegic perfusion

Cardiac protection during transplantation: Intermittent versus continuous cardioplegic perfusion

Insatiable feeding evoked in rats by recurrent perfusion of neuropeptide Y in the hypothalamus

Hyperphagic-like intake of food was determined in the unrestrained rat during the sustained elevation over time of neuropeptide Y (NPY) within the paraventricular nucleus (PVN) and surrounding hypothalamic regions. A single guide tube was implanted stereotaxically in each of 22 rats for localized, intermittent perfusions of a CSF vehicle, nondeprotected NPY(1–36) or native NPY. Each site in the PVN of the fully sated rat was perfused repeatedly over a 5.0-h interval by means of a standard push-pull cannula system at a rate of 20 μl/min for 6.0 min in one of three concentrations: 0.2, 1.0 and 2.0 μg/min. Two perfusions of 1.0 μg/min NPY evoked an intake of 4.6±1.1 g of food over a 3.0-h period, whereas 4–7 and 8–15 perfusions of this concentration of NPY, distributed over 5.0 h, induced the sated rats to eat a total of 12.0±1.1 g and 33.2±3.0 g, respectively. During a fixed number of 10 hypothalamic perfusions distributed over 5.0 h, concentrations of 0.2 and 2.0 μg/min NPY caused a cumulative intake of food in the rats of 14.2±2.0 g and 31.7±3.3 g, respectively. Under each condition, parallel push-pull perfusions of either control solution in the same hypothalamic sites were without effect on feeding. During the 5.0-h interval of repeated perfusions, successive bouts of eating occurred with individual intakes of food reaching as high as 49.0 g, which exceeded by up to two-fold the entire daily consumption of food. However, ingestion of water was unaffected by perfusion of NPY. These results show that unlike the stimulating effects on feeding of other neuroactive factors, NPY creates a hunger which is not satiable as long as the level of NPY in the hypothalamus is chronically elevated over time. Further, should such an elevated level of hypothalamic NPY be maintained, the normal long-term regulation of caloric intake would be displaced, resulting in unremitting overeating and ultimate obesity.

Intermittent perfusion of ischemic myocardium. Possible mechanisms of protective effects on mechanical function in isolated rat heart.

Intermittent restoration of coronary flow during ischemia reduced myocardial damage and improved recovery of function. The mechanisms of the protective effects of intermittent perfusion were investigated in isolated rat hearts. Ventricular function was assessed as the product of developed pressure (left ventricular systolic pressure minus end-diastolic pressure) and heart rate. Recovery of function was calculated by division of the product at the end of reperfusion by that before ischemia. After 40 minutes of sustained global ischemia, intracellular Na+ (Nai) increased from 11 to 74 mumol/g dry wt. During 30 minutes of reperfusion, these hearts took up a large amount of 45Ca2+ (10 mumol/g dry wt), recovered only 24% of preischemic function, and had an increased left ventricular end-diastolic pressure (48 mm Hg). When the 40-minute period of ischemia was interrupted at 10-minute intervals by intermittent perfusion (three periods of 3 minutes) with either oxygenated or hypoxemic buffer, Nai increased to only 12 or 17 mumol/g dry wt, and reperfusion resulted in much lower 45Ca2+ uptake (0.5 and 0.5 mumol/g dry wt, respectively). Recovery of function was 100% of the preischemic value. When hypoxemic buffer without glucose was used for intermittent perfusion, Nai increased to 50 mumol/g dry wt, ATP was depleted, and reperfusion resulted in reduced recovery of function (76%) and moderately increased 45Ca2+ uptake (2.1 mumol/g dry wt). The role of Na(+)-K+ pump activity in maintaining low Nai was assessed by removing K+ from oxygenated or hypoxemic buffers used during intermittent perfusion. Under these conditions, Nai rose to 64 or 102 mumol/g dry wt, 45Ca2+ uptake increased to 4.4 or 9.4 mumol/g dry wt, and recovery of function was poor. There was a highly significant correlation between Nai during ischemia and reperfusion Ca2+ overload (r = 0.87) or impaired recovery of function (r = 0.96). These results indicate that prevention of an increase in Nai by maintenance of Na(+)-K+ pump activity is associated with a reduction of Ca2+ overload through Na+/Ca2+ exchange.

Measurements of blood flow to individual glomeruli in the ophidian kidney

Continuous measurements of the instantaneous rate of blood flow to individual glomeruli in a normal vertebrate kidney were made in the garter snake Thamnophis sirtalis. Epifluorescence video microscopy was used to visualize and record blood flow in the afferent arterioles of superficial nephrons. The dual-slit method was used for the determination of red blood cell (RBC) velocity from the video replay. Simultaneous measurements of the vessel diameter allowed the continuous determination of the instantaneous rate of blood flow. A total of 100 glomeruli was surveyed in 12 animals. These glomeruli displayed both constant and highly variable rates of blood flow, with 21% of all nephrons displaying intermittent glomerular perfusion. The mean single-nephron blood flow rate (SNBFR) for all individuals was 23.9 +/- 10.3 (SD) nl/min (n = 12). The percentage of nephrons with intermittent flow for an individual animal increased significantly with increasing plasma osmolality. Intermittency was associated with low SNBFR values; SNBFR averaged 13.5 +/- 10.2 (SD) nl/min (n = 21) in intermittent nephrons and 29.2 +/- 19.0 (SD) nl/min (n = 79) in continuous flow nephrons, the difference being significant (P less than 0.001). Nephrons with continuous perfusion displayed a much greater range of SNBFR values than intermittent nephrons. This suggests that, although changes in whole kidney glomerular filtration rate (GFR) in reptiles need not involve glomerular intermittency, intermittency may lower GFR.

Fractal Analysis of Vasomotion

Random-like fluctuations have been observed in blood flow in the microvasculature. This we term flow motion, thus distinguishing it from the closely related phenomenon, vasomotion, which refers to fluctuations in vessel diameter. This intermittent perfusion of vascular beds has been observed in skeletal muscle,1 skin,2 mesentery,3 and brain.4 These fluctuations are usually tied to spontaneously occurring rhythmic diameter variations in the feeding arterioles.5 The observations in skeletal muscle microvasculature suggest a relaxation oscillator (pacemaker) behavior with tonic modulation by perfusion pressure.6 The random nature of these fluctuations, which have readily observable periodicities, however, make response measurements difficult in terms of conventional amplitude and frequency changes. Thus, the need exists for improved methods of dealing with such responses. The question that can be asked is whether this randomness represents noise or chaos produced by a low-dimensional nonlinear system.7 The evidence given by our analysis suggests that there may be a low-order chaotic attractor. One cannot make such a conclusion with confidence, however, because the data currently available for the analysis covered only about two minute time periods. While fulfilling the requirements suggested by Grassberger and Procaccia,7 some low-frequency power in the signals would be better analyzed if the data strings were ten times as long.

Vascular washout reduces Ca2+ overload and improves function of reperfused ischemic hearts

Relationships between myocardial Ca2+ uptake, recovery of ventricular function, and restoration of tissue metabolites were determined during 30 min of reperfusion following ischemic and anoxic perfusion with either zero or low coronary flow, zero flow with intermittent perfusion, and low-flow perfusion without substrates. When zero-flow ischemia was maintained for 30 or 40 min, tissue lactate levels increased approximately 100-fold; with reperfusion of these hearts, developed pressure recovered to only 70 and 40% of preischemic function, respectively, and Ca2+ uptake increased by 7- and 15-fold. In contrast, 30 min of low-flow (1 ml/min) anoxic perfusion resulted in accumulation of less lactate (15-fold increase), less reperfusion Ca2+ uptake, and recovery of developed pressure to the preanoxic level. Omission of energy substrates during the low-flow anoxic perfusion caused a reduced recovery of heart rate with lower high-energy phosphate levels and increased Ca2+ uptake, but contractile function recovered to the same extent as in low-flow perfusion with substrate. Even very low flow rates (0.06-0.16 ml/min) of oxygen-deficient perfusate increased high-energy phosphate content and contractile function and decreased Ca2+ uptake. Intermittent perfusion with either oxygenated or anoxic buffer between four 10-min episodes of ischemia reduced lactate accumulation, maintained function, and left Ca2+ uptake essentially unchanged. Recovery of developed pressure during reperfusion was negatively correlated with the amount of lactate that accumulated during ischemia or anoxia and with reperfusion Ca2+ uptake, regardless of the duration or type of ischemia or anoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

The use of fluorescent probes to identify regions of transient perfusion in murine tumors

Sequential intravenous injection of two fluorescent stains, Hoechst 33342 and DiOC7(3), can be used to quantify transient perfusion in experimental tumors. Regions of unmatched staining, indicative of intermittent perfusion, occur when vessels open or close in the 20 minute interval between administration of the dyes. In the murine SCCVII carcinoma, 8.9 ± 2.4% (SD) of vessels in 0.5 g subcutaneous tumors had labelling of adjacent cells with only one stain, suggesting complete vessel closure lasting at least 5 minutes. Regions of intermittent perfusion were not homogeneously distributed throughout the tumor and larger tumors exhibited more mismatch than smaller tumors. Transient: perfusion was observed in both subcutaneous and intramuscular tumor implants and was not significantly affected by restraint of the animal or by ketamine/diazepam anesthesia.

Prostanoid Release from Ex Vivo Perfused Canine Arteries and Veins: Effects of Prolonged Perfusion, Intermittent Perfusion, as well as Exposure to Exogenous Arachidonic Acid, Thrombin and Bradykinin

Regulation of prostanoid release from ex vivo perfused vessel segments is not fully understood. A series of perfusion experiments were performed with canine arteries and veins to define certain regulatory phenomena. Arteries were perfused with pulsatile flow of 90 ml/min at a pressure of 100 mmHg, and veins with nonpulsatile flow of 90 ml/min at a pressure of 7 mmHg. Segments were perfused with Hanks' balanced salt solution for five 15-min periods with the perfusate exchanged after each study period. With onset of perfusion, there was an initial burst of prostacyclin release to 127 +/- 40 pg/mm2, declining to 32 +/- 10 pg/mm2 after 60 minutes (p less than 0.005). If perfusion continued for 5.5 hours, there was a stable release period between 1 and 3 hours, followed by a very slow decline. At that time addition of arachidonic acid (AA) increased prostacyclin release six-fold (p less than 0.01). Vessels perfused for 1 hour and then rested for another hour, responded to reperfusion at the second onset of flow with a two-fold increase in prostacyclin release (p less than 0.01). Vessels perfused with thrombin, bradykinin or AA (either added to each perfusate or only to the last perfusate) exhibited greater prostacyclin release than did control segments. Release of thromboxane steadily declined with time in all parts of the study, and only increased with the addition of AA to the perfusate.(ABSTRACT TRUNCATED AT 250 WORDS)

間欠的逆行性脳潅流下ｏｐｅｎ ｔｅｃｈｎｉｑｕｅによる大動脈弁閉鎖不全を伴ったＤｅＢａｋｅｙ ＩＩＩ型逆行性大動脈解離に対する血行再建術

間欠的逆行性脳潅流下ｏｐｅｎ ｔｅｃｈｎｉｑｕｅによる大動脈弁閉鎖不全を伴ったＤｅＢａｋｅｙ ＩＩＩ型逆行性大動脈解離に対する血行再建術

Comparison of Intermittent Warm and Cold Blood Perfusion During Hypothermic Myocardial Preservation on Functional and Metabolic Recovery

Abstract Numerous techniques are used to maintain intraoperative heart viability. The studies presented here evaluated heart function and metabolism after various periods of preservation up to 4 hours with intermittent warm and cold blood perfusion. Using a heterotopic heart model cooled to 10°C and maintained for 1, 2, 3, and 4 hours, various preservation techniques were compared. Changes in myocardial metabolism were determined from substrate uptakes and biopsy samples of the left ventricular muscle for high‐energy phosphates. Preservation techniques included: (1) sustained hypothermia, (2) 1 or 2 hours of sustained warm blood perfusion with fibrillation, (3) intermittent cold blood perfusion during 2, 3, and 4 hours of preservation, (4) intermittent warm blood perfusion during 2, 3, and 4 hours of preservation and (5) a control group (no preservation). Normothermic fibrillation had no effect on postpreservation functional or metabolic parameters. Sustained hypothermia reduced functional recovery proportional to the length of ischemia. The cold intermittent procedures maintained function and metabolism better than sustained hypothermia, while warm intermittent preservation maintained function and metabolism at control levels throughout the recovery period for all preservation techniques. Changes in ATP mirrored the functional changes. Creatine phosphate (CP) was markedly reduced during heart isolation and preservation and exceeded the control by 100% during reperfusion. For operative procedures of 2 hours or less, functional and metabolic recovery was not affected by the various preservation methods applied. Warm intermittent perfusion during hypothermic preservation offered the best protection for the myocardium. The warming cycles during hypothermia may provide some degree of preconditioning and protect the myocardium during reperfusion.

Natural defense mechanisms during ischemia.

Mechanisms are described that are known to prolong survival of ischemic myocardium. Some of these mechanisms are species-specific: collateral blood flow does not contribute to survival in rats, rabbits, and pigs but it salvages subepicardial myocardium in the dog and probably in man. The most important defense mechanism is enlargement of collaterals by growth of pre-existing smaller vessels. This process is not operative in sudden coronary occlusion but may save a substantial portion of the myocardium if occlusion occurs more slowly, i.e. several days up to a week. Experimental evidence is presented that thrombotic occlusion, clot-retraction, and partial clot lysis by endothelium can be sufficiently dynamic to allow intermittent myocardial perfusion and to permit collaterals to grow. The glycogen stores of the heart are of limited importance. They are useful for glycolytic ATP-production, the limitation is imposed by the inhibition of glycolysis in ischemia due to unfavourable pH and lack of NAD. Some beta-blockers do interfere with glycogenolysis in the heart. The cardioprotective role of adenosine needs further study. An interesting concept is the change in resistance to ischemia after repeated cycles of ischemia. It is not known at present whether repeated cycles will increase or decrease the myocyte's resistance against ischemia.

Erratum

Free AccessErratumPublished Online:28 Jan 2014https://doi.org/10.1259/0007-1285-54-647-1013-cSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail AboutAbstractA catheter system for the safe and efficient delivery of tissue glues (bucrylate) for visceral embolization (M. S. Khangure, H. T. ApSimon, T. M. H. Chakera and D. E. Hartley), The British Journal of Radiology, August 1981, 54, 671–673.We regret that the caption to Figure 3 (p. 672) is incorrect. It should read:Assembled catheter arrangement. (1) The balloon and tip of balloon catheter unit introduced coaxially through the guiding catheter. (2) The guiding catheter. (3) Teflon introducer sheath. (4) Y connector attached to introducer sheath. The straight limb allows the introduction of the guiding catheter. The side arm is used to flush the sheath intermittently with heparinized saline. (5) Y connector attached to the end of the guiding catheter. The straight limb is used for the introduction of the balloon catheter unit. (6) The side arm is used for the intermittent perfusion of heparinized saline into the guiding catheter. (7) 1 ml syringe containing contrast medium for balloon catheter. (8) 1 ml syringe containing opacified bucrylate. (9) Two way tap used to keep balloon inflated. Previous article Next article FiguresReferencesRelatedDetails Volume 54, Issue 647November 1981Pages: 927-1026 © The British Institute of Radiology History Published onlineJanuary 28,2014 Metrics Download PDF

Concentrations of semi-synthetic penicillins in the plasma and in the expectoration, administered by means of intermittent vein perfusion.

We report the levels of concentration of ampicillin, dicloxacillin, and carbenicillin reached in the blood and in the expectoration following the administration of these drugs by rapid venous infusion, once every 24 h. The concentration of ampicillin in the blood serum varied from 150 to 180 micrograms/ml at the end of the infusion and from 30 to 3 micrograms/ml 4 afterwards and the dicloxacillin concentration from 150 to 120 micrograms/ml, and from 24 to 6 micrograms/ml. The concentration of ampicillin in purulent expectoration was 5-7 micrograms/ml and that of dicloxacillin 2.5-4 micrograms/ml. The concentration of carbenicillin in the plasma varied from 1,040 to 130 micrograms/ml, and in the expectoration it was around 15 micrograms/ml. Several cases of acute and chronic lung and bronchial diseases caused by bacteria have been treated by means of venous infusion once every 24 h and results were excellent.

The Effects of Perfusion on an Amputated Extremity

The amputated hindquarters of adult female rats were infused with solutions of lactated Ringer's, Collins hypertonic renal perfusate, and dextran-dextrose on a washout and continuous basis. The perfusate was analyzed for energy compounds and breakdown products and the muscle tissue examined histologically. Intermittent perfusion or injection under pressure led to marked edema in a 4-hour period and was abandoned in favor of a system that perfused the part at 120 to 150 cm H2O. The model perfused with Collins gained an average of 1.35 gm, that with lactated Ringer's 2.35 gm, and that with dextran-dextrose lost 2.35 gm. Pressure graphs of the various solutions indicated that the vascular bed reacts more physiologically to Collins solution and dextran-dextrose than to lactated Ringer's. Histologic sections of the muscle biopsies confirmed this. The release of ATP and hypoxanthine with lactated Ringer's suggests that it is the most damaging of the perfusates. These findings support the results of the pressure graphs and histologic studies. A potential for replantation of amputated limbs that contain muscle when the cold ischemia time may exceed 6 hours is suggested by the data presented.

Ultrastructural and cytochemical correlates of myocardial protection by cardiac hypothermia in man

We report observations on ultrastructural and cytochemical changes in the myocardium after hypothermic protection in 21 patients who underwent cardiac operation. Two general categories of hypothermic protection were studied. (1) topical cooling during anoxic arrest and moderate general hypothermia (10 patients with aortic valve replacement, Group 1) and (2) intermittent perfusion during moderate general hypothermia combined with topical cooling (11 patients with multiple valve replacement, Group II). Transmural left ventricular biopsies were taken at the start of the cardiopulmonary bypass and shortly after the end of aortic cross-clamping. In Group I (cross-clamp time, 51 +/- 12 minutes) only minor pathologic changes of the myocardial fine structure were found, with no differences among the left ventricular layers. In most mitochondria, structure remained intact but the mitochondrial granules disappeared. Cytochrome-c-oxidase activity was unchanged. In Group II (total cross-clamp time, 83 +/- 16 minutes) the subendocardium was well preserved. Slight subcellular damage comparable with that of resulting from topical cooling was seen in all hearts even after a total cross-clamp period of 106 minutes. Cytochrome-c-oxidase activity was unchanged. In the subepicardium, however, a positive correlation was found between the severity of ultrastructural damage and total cross-clamp time (p less than 0.05). Matrix clearing, damage to the cristae and the mitochondrial membranes, and nuclear abnormalities occurred when the aorta was cross-clamped for morethan 60 minutes. Cytochrome-c-oxidase activities decreased in these samples. It is concluded that: (1) no significant subcellular injury was found in hearts cooled topically during 1 hour of anoxic arrest; and (2) in hearts protected by intermittent perfusion during moderate general hypothermia and additional external cooling, the subendocardium was well preserved for anoxic periods of up to 106 minutes. However, after 60 minutes of aortic cross-clamping subcellular damage increased progressively in the subepicardium.

Intensive therapy of acute hepatic insufficiency in dogs by heterotopic liver allotransplant

The efficacy of heterotopic liver transplantation to support life and to correct metabolic disturbances in the presence of acute hepatic failure was tested in 70 dogs. Acute hepatic failure was induced by two-stage ischaemic damage to the animals' livers and by biliary obstruction. The donor liver was stored for 3 h by the method of intermittent perfusion. The graft was placed in the right paravertebral gutter. The inflow was arterial only. No immunosuppressive agents were administered. During the postoperative period the main biochemical indices decreased and returned to almost normal values by the fourth day. The auxiliary liver was able to correct the clotting of blood. There was significant regression of encephalopathy, which was confirmed by encephalographic monitoring. Special attention was paid to the adaptation of the stored graft after revascularization. Resuscitation from hepatic failure and subsequent survival of transplanted animals confirmed the significant therapeutic effect of heterotopic allotransplant.

Myocardial protection by intermittent perfusion with cardioplegic solution versus intermittent coronary perfusion with cold blood

The myocardial protection provided by cardioplegic solution using buffered, isosmotic potassium (30 mEq. per liter) was compared with intermittent cold coronary perfusion for 2 hours of aortic cross-clamping in dogs. The cardioplegic solution (Group CS) or cold blood (Group CB) was infused every 15 minutes through a cooling coil to reduce the perfusate temperature to 5 degrees C. Myocardial function after 30 minutes of reperfusion and rewarming was reduced in Group CB with a significant reduction in peak systolic pressure at a left ventricular (LV) balloon volume of 20 ml. and a significant reduction of dp/dt. In contrast, in Group CS, LV function was unchanged from the base-line period. LV compliance also was significantly reduced in Group CB while being unchanged in Group CS. Myocardial extravascular water content, obtained by dessication, was significantly higher in Group CB than in Group CS, which may explain the reduction in compliance. Electron microscopy showed normal ultrastructure in Group CS but extracellular edema in Group CB. Total coronary blood flow showed a sustained increase during reperfusion in both groups. Oxygen consumption rose with rewarming to base-line levels in both groups, whereas lactate and pyruvate consumption was reduced in both groups, particularly Group CB. Cardioplegic solution thus appears to be superior to the intermittent perfusion of cold blood for myocardial protection. The addition of potassium arrest, by markedly reducing myocardial metabolism, improves the protection afforded by cold blood perfusion alone.

Myocardial preservation during aortic valve surgery: Assessment of five techniques by cellular chemical and biophysical methods

Five different types of myocardial protection were employed in this series of 168 patients undergoing aortic valve replacement. Two methods of assessing myocardial preservation were used: cellular biological estimations and quantitative polarization measurements. Both parameters showed that either of two methods, continuous perfusion at 32 degrees C. with a beating heart or cardioplegic hypothermic arrest, protected the myocardum best. Intermittent perfusion at 30 degrees C. with a fibrillating heart was the worst means of preservation. Our investigations (both clinical and experimental) have also shown that changes in birefringence, indicative of deteriorating myocardial function, are often detectable before parallel cytochemical changes are apparent.

Perfusion in the experimental preservation of the rat heart.

Rat hearts have been preserved for 24 hours using four different preservation solutions. The results suggest that the best preservation fluid is Tyrode's solution with Ficoll 5 per cent. A comparison of simple cooling of the heart and perfusion, either continuous or intermittent, has shown that intermittent perfusion of the heart for 2 minutes every 6 hours gives the highest rate of 24-hour preservation.