Hypothermic Reperfusion Research Articles

Transient hypothermic reperfusion and postischemic recovery in isolated rat heart

Transient hypothermic reperfusion and postischemic recovery in isolated rat heart

Hypothermia prevents increased capillary permeability following ischemia-reperfusion injury

Severely injured trauma victims are frequently hypothermic. It is nuclear, however, whether hypothermia itself is a detrimental or protective physiologic response to injury. One of the major consequences of fluid resuscitation following ischemic injury is edema formation, characterized by ischemia-reperfusion injury models. The purpose of this study was to examine the effect of regional hypothermia on a feline intestinal model of ischemia-reperfusion injury. An autoperfused segment of cat ileum was isolated and arterial, venous, and lymphatic vessels were cannulated. Lymph flow ( Q l), lymph ( C 1), and plasma ( C p) protein concentrations and segmental blood flow ( Q b) were measured. Permeability changes were characterized by the minimal C l C p ratio obtained by elevating venous outflow pressure. Animals were divided into the following groups: Group I: 1 hr of intestinal ischemia (30 mm Hg) with autoreperfusion; Group II: 1 hr of intestinal hypothermia (28°C) with subsequent rewarming; Group III: 1 hr of combined ischemia and hypothermia. Group III animals were either kept hypothermic (IIIA) or rewarmed (IIIB) during autoreperfusion. Minimal C l C p ratios (mean ± SEM) were as follows: Control: 0.15 ± 0.02; Group I∗: 0.32 ± 0.03; Group II: 0.15 ± 0.01; Group IIIA: 0.18 ± 0.02; Group IIIB∗: 0.42 ± 0.02; ( ∗ = P < 0.01 vs control). Reperfusion flow rates were no different between Group IIIA and Group IIIB animals. Ischemia-reperfusion, but not hypothermia alone, caused a marked increase in intestinal capillary permeability. Permeability increased after combined ischemia and hypothermia only if reperfusion was accompanied by rewarming. Hypothermic reperfusion protected against the increased permeability following ischemia.

Relationship between the high-energy phosphate content and various left ventricular functional parameters of the normal and hypertrophied heart after global ischemia and reperfusion.

Using an isolated rat heart preparation (Langendorff perfusion, perfusion pressure 100 cm H2O) the correlation between the high-energy phosphate content and various left ventricular (lv) functional parameters of the hypertrophied heart (spontaneous hypertensive rats lv/body weight ratio 3.6 +/- 0.5 x 10(-3) was determined after normo- (30 min) and hypothermic (25 degrees C, 120 min) cardioplegic arrest and reperfusion, and compared with normal hearts (Wistar rats lv/body weight ratio 2.0 +/- 0.3 x 10(-3). St. Thomas Hospital solution was used as the cardioplegic agent. Before ischemia hypertrophied hearts had a significantly higher developed left ventricular pressure, pressure rate product and dp/dtmax, but a significantly lower ATP and total adenine nucleotide content. Irrespective of the mode and temperature of cardiac arrest there was a strong correlation both for normal and for hypertrophied hearts between the high-energy phosphate content expressed as ATP, total adenine nucleotides or the "energy charge" and the left ventricular functional parameters pressure rate product and dp/dtmax. The correlation coefficient ranged from 0.80 to 0.89 and was highest when the ATP content was plotted against pressure rate product (r = 0.89). There was a different slope for normal and hypertrophied hearts with a steeper decline of the left ventricular function in hypertrophied hearts for any given reduction of the myocardial adenine nucleotide content. Our results indicate that a similar reduction of the ATP or total adenine nucleotide content in both the normal and hypertrophied heart reduces left ventricular function to a greater degree in the hypertrophied heart.

The effect of hypothermia during the period of calcium repletion on the calcium paradox

Reperfusion of an isolated heart with a calcium-containing solution after a short calcium-free perfusion may result in irreversible cell damage: the calcium paradox. In this investigation the effect of hypothermia during reperfusion with calcium-containing solution on the calcium paradox damage in the isolated rat heart was studied. In addition, the effect of pre-cooling the heart during the calcium-free period was investigated. Creatine kinase release was used to define cell damage. Normothermic (37 degrees C) calcium-free perfusion followed by normothermic reperfusion with calcium-containing solution resulted in a massive release of CK. When the normothermic calcium-free perfusion was followed by hypothermic (10 degrees C) calcium-containing reperfusion, CK release was reduced by 20% (P less than 0.005). This CK release during reperfusion was further reduced by 55% and 80% when the normothermic calcium-free perfusion was followed by 5 or 10 min respectively of hypothermic calcium-free perfusion prior to the hypothermic calcium-containing reperfusion. The results show that hypothermia during the period of calcium repletion retards the sequence of events which ultimately results in release of large amounts of intracellular components.

Effect of initial reperfusion temperature on myocardial preservation

The effect of initial postischemic reperfusion temperature on myocardial preservation was studied in the isolated working rat heart model. After baseline measurement of aortic flow rate, coronary flow rate, and heart rate, 40 hearts were subjected to 60 minutes of ischemic arrest at 15 degrees C induced with a single dose of cold potassium cardioplegic solution. Hearts were then revived with a 10 minute period of nonworking reperfusion at 28 degrees, 31 degrees, 34 degrees, or 37 degrees C (10 hearts each), followed by 5 minutes of nonworking reperfusion at normothermia, followed by 30 minutes of working perfusion. Repeat measurements of function were obtained and postischemic release of creatine kinase into coronary effluent was determined. Recovery of aortic flow was significantly reduced at lower initial reperfusion temperatures (75% at 28 degrees C versus 88% at 37 degrees C) and the effect was approximately linear throughout the range studied (p less than 0.05). Release of creatine kinase into coronary effluent was greater at lower initial reperfusion temperatures (421 ImU/min/gm wet weight at 28 degrees C versus 115 ImU/min/gm wet weight at 37 degrees C), also in a linear manner (p less than 0.05). In this model, initial postischemic hypothermic reperfusion is deleterious to cellular integrity and functional recovery of the preserved myocardium. Studies in higher animals and humans are warranted to further evaluate the effect of initial reperfusion temperature on myocardial preservation.

Substance P- and leu-enkephalin-immunoreactive nerves before and after myocardial ischaemia, hypothermic chemical cardioplegia and reperfusion injury during open-heart surgery

During open-heart surgery, myocardial biopsies were obtained before the start of extracorporeal circulation (from the right auricular appendage) and after weaning from the pump (from the right atrium), and processed for immunocytochemical demonstration of substance P- and leu-enkephalin-immunoreactive nerve fibres and for electron microscopy. Substance P-immunoreactive nerves were seen around blood vessels, between myocardial cells and forming large glomerulus-like loops, but were not numerous. Leu-enkephalin-immunoreactive nerves were very sparse. We therefore believe that both nerve types primarily are modulatory axons. In the post-weaning specimens, nerves of both types were more numerous (attributable to the different site of biopsy), and no change was seen in the immunofluorescence reaction. The ultrastructure (all types) of nerve terminals was well preserved, although myocardial damage was obvious in many specimens. Cardiac nerves, including peptidergic nerves, thus seem to be relatively resistant to ischaemia, hypothermic chemical cardioplegia and reperfusion injury.

The temperature dependence of recovery of metabolic function following hypothermic potassium cardioplegic arrest

A study was performed to define the influence of reperfusate temperature on the recovery of high-energy phosphate compounds following hypothermic ischemic cardioplegic arrest. Two groups, each consisting of six pigs, were subjected to 1 hour of hypothermic potassium cardioplegic arrest (myocardial temperature 10 degrees to 15 degrees C). In one group, the arrest period was followed by a 30 minute period of normothermic reperfusion (37 degrees C) followed by a second hour of hypothermic cardioplegic arrest and a second 30 minute normothermic reperfusion period. The second group of pigs was reperfused after the first hour of arrest for 30 minutes with a cold blood (10 degrees to 14 degrees C) followed by an additional hour of hypothermic cardioplegic arrest and a second 30 minute hypothermic reperfusion period. Myocardial biopsy specimens for adenosine triphosphate (ATP) and creatine phosphate (CP) were obtained at the beginning of perfusion (control studies), at the end of each hour of the arrest interval, and at the end of each 30 minutes of reperfusion. The ATP and CP levels were significantly higher after normothermic reperfusion than after hypothermic reperfusion. After normothermic reperfusion the CP level exceeded control; following hypothermic reperfusion CP remained less than 70% of the control level. On the basis of these results, it is proposed that hypothermic reperfusion does not permit the same level of high-energy phosphorylation that is provided with normothermic reperfusion and may therefore adversely affect hemodynamic recovery of the heart after cardioplegic arrest.

Description and interpretation of morphological changes in canine kidneys after preservation with hypothermic solutions and subsequent reperfusion

The morphological appearance of canine kidneys preserved with hypothermic solutions of three different types (Rheomacrodex, Collins 3 and Sacks-II) was studied in acute autologous reperfusion models. While at the end of preservation the renal structure still seemed intact (with the exception of the Rheomacrodex model), reperfusion was associated with the manifestation of hitherto latent structural lesions. This is confirmed by light-microscopic features (hydropic swelling and destruction of the tubular epithelium), enzyme histochemical studies (positive alkaline phosphatase reaction of the Bowman space) and topo-optical reactions (loss of anisotropy of the cytomembranes in the presence of fairly well preserved birefringence of the basement membranes).