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The use of frozen intravenous crystalloid solutions as the refrigerant for shipping blood.

The authors studied whether cooled sterile intravenous crystalloid solutions could be used to refrigerate red cells during shipment. Six 1000-ml bags of 0.9 percent normal saline and lactated Ringers (RL) solutions were supercooled and tested separately at temperatures ranging from 1 to -78 degrees C, with either 5 or 30 units of packed red cells (PRBCs). The PRBCs were shipped in a standard military container that permitted separation of the supercooled solutions from the PRBCs. Cooling RL solutions to 6 degrees C and to -22 degrees C maintained acceptable storage temperatures of the PRBC for 36 and 50 hours, respectively, and did not cause visible damage to the units. No significant changes were observed in various biochemical measurements of the cells and plasma. Cooling the RL solution to -78 degrees C caused a significant (p less than 0.05) increase in plasma potassium concentration. The effectiveness of the crystalloid solutions in refrigerating blood varied with the ratio of the number of PRBCs to the volume of cooled solutions and with the ambient temperature surrounding the container. The results of this study suggest that cooled intravenous crystalloid solutions can be used as refrigerants for PRBCs during shipment.

Blood Preservation↗

A paradigm for consensus. The University Hospital Consortium guidelines for the use of albumin, nonprotein colloid, and crystalloid solutions.

OBJECTIVE: To develop contemporary, comprehensive guidelines for the appropriate and efficient use of albumin, nonprotein colloid, and crystalloid solutions. DESIGN: A systematic, literature-based, consensus exercise employing a modified Delphi method. PARTICIPANTS: Thirty-one medical and allied health professionals from 26 University Hospital Consortium (Oak Brook, Ill) member institutions were initially chosen to participate. Participants were selected on the basis of their recognized research in the use of albumin, nonprotein colloid, and crystalloid solutions, and/or experience in the review of appropriateness of such use. A total of 24 participants completed the exercise. MAIN OUTCOME MEASURES: Group responses were statistically analyzed in an iterative consensus development process. Five separate questionnaire rounds were designed to establish criteria for the appropriate use of albumin, nonprotein colloid, and crystalloid solutions. RESULTS: Consensus guidelines were developed outlining the appropriate use of these products for 12 clinical indications, including hemorrhagic shock, nonhemorrhagic (maldistributive) shock, hepatic resection, thermal injury, cerebral ischemia, nutritional intervention, cardiac surgery, hyperbilirubinemia of the newborn, cirrhosis and paracentesis, nephrotic syndrome, organ transplantation, and plasmapheresis. CONCLUSIONS: The Delphi method, a systematic, literature-based consensus process, was shown to be useful in the development of complex clinical practice guidelines for the use of albumin, nonprotein colloid, and crystalloid solutions. It is anticipated that the guidelines will assist health care providers to develop local institutional policies and procedures for the appropriate and efficient use of albumin and albumin alternatives. Institutions reviewing and updating existing local guidelines may use the University Hospital Consortium guidelines as a model for comparison.

Academic Medical Centers↗

An assessment of crystalloid solutions for donor heart preservation.

The optimal technique for donor heart protection remains controversial. One component of preservation is the transport solution. Although saline solution is most frequently used as a transport medium, other crystalloid solutions may be superior. Accordingly, human right atrial trabeculae contracting isometrically in vitro were used to assess five crystalloid solutions at two different temperatures (12 degrees and 4 degrees C): St. Thomas' Hospital solution, modified Krebs-Henseleit (K+ = 16 mEq/L), Krebs-Henseleit (K+ = 4.5 mEq/L, saline, and Euro-Collins. After a 24-hour preservation period the muscles were restimulated at 34 degrees C and recovery of function was monitored for 30 minutes. Recovery of developed force was not affected by temperature (p = 0.13 by two-way analysis of variance). However, St. Thomas' Hospital solution provided the best recovery of developed force (103.3 +/- 6.2% of control) compared with saline, which had the worst developed force (2.8% +/- 1.3%) (p less than 0.002). Modified Krebs-Henseleit, Krebs-Henseleit, and Euro-Collins demonstrated intermediate performance. Although there were no differences between groups in recovery of resting force, it was greater in all groups with muscles cooled to 4 degrees C (238.7% +/- 17.6% of control) (p less than 0.001). Dry/wet weight ratios did not demonstrate statistically significant differences between groups. We conclude that, of the solutions tested, St. Thomas' Hospital solution provides the best preservation of atrial myocardium. Storage in crystalloid solutions leads to impaired relaxation, which is more apparent in tissue cooled to 4 degrees C and does not appear to be solely due to increased tissue swelling.

Evaluation Studies as Topic↗

Effects of crystalloid solutions on circulating lactate concentrations: Part 1. Implications for the proper handling of blood specimens obtained from critically ill patients.

OBJECTIVES: a) To test the hypothesis that circulating lactate concentrations are the same in simultaneously collected arterial and central venous blood specimens; b) to test the hypothesis that even small amounts of crystalloid solutions, which are inadequately "cleared" from these indwelling arterial and venous catheters, can lead to clinically important and misleading changes in the measured lactate values. DESIGN: A prospective, multiexperiment study. SETTING: A critical care research laboratory and a 20-bed intensive care unit (ICU). PATIENTS: Three hundred fifty-five patients. INTERVENTIONS: Blood samples were collected. MEASUREMENTS AND MAIN RESULTS: Experiment 1: Simultaneously collected arterial and central venous blood specimens were obtained on 148 occasions from 48 medical ICU patients receiving no lactated Ringer's solution (RL). Arterial and central venous lactate values were nearly identical in these patients. The correlation between the arterial and central venous lactate concentrations was excellent (r2 = .85; p < .0001) and the agreement between the arterial and central venous lactate concentrations was also excellent (bias and precision = 0.04 mmol/L and +/- 0.38 mmol/L, respectively). Experiment 2: Arterial and mixed venous blood samples were obtained from 100 percutaneous transluminal coronary angioplasty (PTCA) and 75 cardiac surgical patients immediately before the performance of these cardiac procedures. We found the central venous lactate concentrations to be higher than arterial lactate values in the cardiac surgical group, and there was a very poor correlation (r2 = .07) between arterial and central venous lactate values in the cardiac surgical group. The correlation between central venous and arterial lactate concentrations in the PTCA patients was excellent (r2 = .84) and similar to the findings of experiment 1. Since the cardiac surgical patients received RL and the PTCA patients received no RL, we speculated that the intravenous infusion of RL in the cardiac surgical group accounted for these discordant findings. To test this speculation, we performed experiments 3 and 4. Experiment 3: In a large bench study, blood specimens were divided into multiple 1-mL aliquot portions, to which 0.01, 0.05, 0.10, 0.50, or 1.0 mL of various crystalloid solutions, containing or not containing RL, were added. In a volume-dependent and linear manner, solutions containing RL increased the circulating lactate concentration from 10% to > 400% of the baseline lactate value. In a volume-dependent and linear fashion, the non-RL crystalloid solutions decreased the lactate concentration by 0 to 66% of the baseline nondiluted lactate concentration. Experiment 4: In 30 different cardiac surgical patients, we simultaneously obtained central venous and arterial blood specimens. Patients this time received no RL, and catheter lines were adequately cleared (removal > 5 mL) of crystalloid solutions. We found a correlation (r2 = .82; p < .0001) that was virtually identical to the findings of experiment 1 and to the findings in the PTCA group of experiment 2. CONCLUSIONS: a) Arterial and central venous lactate concentrations are similar in hemodynamically stable critically ill patients, b) Even small amounts of RL-containing solutions in catheters used for blood sampling may cause false increases in the circulating lactate concentration. c) Even small amounts of non-RL crystalloid solutions in catheters used for blood sampling may falsely decrease circulating lactate values. d) When blood specimens are drawn from indwelling catheters, all crystalloid solutions must be cleared from the line.

Blood Specimen Collection↗

Reversal of bupivacaine epidural anesthesia by intermittent epidural injections of crystalloid solutions.

This study was designed to determine whether epidural motor blockade could be reversed by postoperative injections of crystalloid solutions via the epidural catheter. Twenty-seven patients (ASA physical status I, nonlaboring) had epidural anesthesia with 0.75% bupivacaine for elective cesarean delivery. Postoperatively, patients were randomized to receive three 15-mL injections (over 30 min) of crystalloid solutions (normal saline or Ringer's lactate) or no treatment (control) via the epidural catheter. Degree of motor and sensory blockade was evaluated with an investigator blinded to treatment group. Rate of resolution of sensory blockade was not different among groups. However, time for resolution of motor blockade was more than twice as long in the control group than in either treatment group (control = 178 +/- 70 min vs Ringer's lactate = 84 +/- 44 min, normal saline = 70 +/- 38 min, P = 0.001). The data suggest that unwanted motor blockade due to epidural anesthesia can be reversed by epidural injections of crystalloid solutions.

Adult↗

Long-term hypothermic preservation of cardiac myocytes isolated from the neonatal rat ventricle: a comparison of various crystalloid solutions.

In this study, the functional and biochemical effects of crystalloid solutions on immature cardiac myocytes incubated under hypothermic conditions were evaluated. Cardiac myocytes were isolated from neonatal rat ventricles and cultured for 4 days, following which 12.5 x 10(5) myocytes per flask were incubated at 4 degrees C for 3, 6, 12, and 18 h in five types of crystalloid solutions: lactated Ringer's (LR), St. Thomas' Hospital (ST), University of Wisconsin (UW), 5% glucose-based potassium (GK), and normal saline (NS). The levels of creatine phosphokinase (CPK) and lactate dehydrogenase (LDH) in the solutions were measured after each hypothermic incubation, following which the myocytes were cultured for an additional 24 h at 37 degrees C to evaluate the recovery of the myocyte beating rate. In the LR, UW, and NS groups, the recovery ratios of the myocyte beating rate were over 95% of the control (the beating rate prior to hypothermic incubation) at 3 h, but decreased to 20.3, 15.1, and 0%, respectively, at 18 h. The ST and GK groups had significantly lower recovery ratios than the other three groups (72.9% and 63.4%, respectively) at 3 h. The release of CPK and LDH in the LR, UW, and NS groups was significantly suppressed compared to the ST and GK groups, with the greatest suppression observed in the LR group. Moreover, the ST and GK groups had the highest CPK and LDH levels, respectively. Thus, LR solution had the least cytotoxic effects, indicating that it could be the most suitable basic solution of the various cardioplegic or preservation solutions during the neonatal period.

Adenosine↗

The rates of adhesion development and the effects of crystalloid solutions on adhesion development in pelvic surgery.

OBJECTIVE: To document rates of adhesion development after abdomino-pelvic surgery, stratified by adhesion type, access method, and use of crystalloid solution instillates. DESIGN: Reports from a MEDLINE search (1/1/1966-12/18/1996) detailing rates of adhesion development and meeting the inclusion criteria were subjected to meta-analysis. SETTING: Meta-analysis. PATIENT(S): Patients undergoing abdomino-pelvic surgery. INTERVENTION(S): Intraperitoneal crystalloid solution instillates. MAIN OUTCOME MEASURE(S): Percentage adhesion-free outcome in patients ("patients") or surgical sites ("sites"). RESULT(S): Adhesion-free outcome (sites) was lowest for reformed (26.3% laparotomy; 14.3% laparoscopy), higher for de novo 1b (direct trauma) (45.2% laparotomy, 37.2% laparoscopy), and highest for de novo 1a (indirect trauma) adhesions (82.4% laparoscopy). Crystalloid solution instillates reduced adhesion-free outcome at sites (45.2% versus 20% de novo 1b adhesions in laparotomy) and in patients (43.5% versus 19.9% reformed, laparotomy; 71.7% versus 25% de novo 1b, laparoscopy). CONCLUSION(S): Adhesion-free outcome was lowest for reformed, higher for de novo 1b, and highest for de novo 1a adhesions. Surprisingly, it was lower in laparoscopy than in laparotomy for de novo 1b and reformed adhesions. Crystalloid instillates did not increase adhesion-free outcome. Although limited by the retrospective and heterogeneous nature of the data, these conclusions nonetheless provide a basis on which to formulate future hypotheses.

Crystallization↗

Influence of a long-term, high-dose volume therapy with 6% hydroxyethyl starch 130/0.4 or crystalloid solution on hemodynamics, rheology and hemostasis in patients with acute ischemic stroke. Results of a randomized, placebo-controlled, double-blind study.

BACKGROUND: This study was performed to investigate the clinical effects of a 4-day volume therapy with a newly developed, 6% hydroxyethyl starch (HES) 130/0.4 versus crystalloid solution, with particular regard to systemic and cerebral hemodynamics, rheology and safety. METHODS: In a randomized, double-blind study, 40 patients suffering from an acute ischemic stroke received either 6% HES 130/0.4 or crystalloid solution as continuous infusion over 4 days with a total dose of 6.5 liters. Efficacy parameters studied included hemodynamics (cardiac output, blood pressure, flow velocity with transcranial Doppler) and rheology (hematocrit and plasma viscosity). Safety parameters examined included laboratory, hemostaseology (including factor VIII) and an adverse event questionnaire (including pruritus). RESULTS: In both groups, a small, but not significant increase in cardiac output was observed. There were no significant changes regarding the remaining efficacy or safety parameters, except for the well-known increase in serum alpha-amylase through the infusion of HES. CONCLUSION: In our study with patients suffering from acute ischemic stroke, continuous infusion (1 ml/min) of HES 130/0.4 or crystalloid solution did not differ regarding safety or hemodynamic efficacy.

Brain Ischemia↗

Effects of intravascular perfusion of cooled crystalloid solution on cold-induced brain injury using an extracorporeal cooling-filtration system.

BACKGROUND: We evaluated cerebral metabolic change during brain hypothermia with intravascular perfusion of cooled crystalloid solution using an extracorporeal cooling-filtration system and cerebroprotective effects of this hypothermia on brain injury in an animal model. METHOD: Microdialysis probes were implanted into the bilateral parietal cortices. A cold-induced brain injury was produced behind the microdialysis probe on the right parietal cortex. Immediately after injury in the cooled group (n=9), Ringer's solution cooled to 5 degrees C was infused into the right vertebral artery after occlusion of the bilateral common carotid and the left vertebral arteries. Excessive fluid was ultrafiltrated by a dialyzer. Brain temperature was maintained at about 20 degrees C for 60 minutes. In 7 dogs, three neck arteries were occluded for 60 minutes after injury without cooled fluid infusion. The extracellular concentrations of glutamate, lactate, and pyruvate were measured serially for 180 minutes after injury. FINDINGS: Extracellular glutamate concentrations in the cooled group did not increase, while there was a significant increase in the injured hemisphere as compared to the uninjured hemisphere in the non-cooled group ( P<0.05). Extracellular lactate concentrations increased slightly after occlusion in both groups. The depth of cortical injury was limited in the cooled group, but extended into the white matter in the non-cooled group up to 240 minutes after injury. INTERPRETATION: Occlusion of three main arteries induced ischaemia under critical threshold in canine brains. Under this condition, intravascular cooling with crystalloid solution suppressed accumulation of extracellular glutamate and reduced tissue damage in the early phase after cold-induced brain injury, as cerebroprotective effects. This information suggests that a method employing brain hypothermia via intra-arterial cooling with an extracorporeal cooling-filtration system has potential to achieve successful, safe, selective brain cooling.

Animals↗

[Comparative evaluation of the effects of crystalloid solutions containing sodium lactate and sodium succinate on the hemodynamic indicators in different types of hemorrhage].

The results are presented of the hemodynamics investigations under the influence of two saline infusion solutions in varying types of hemorrhage. The suggested crystalloid solution succinasol contains sodium succinate (instead of lactate that is present in lactasol) which improves energetic processes in tissues under conditions of circulatory hypoxia. The results of the study of hemodynamics parameters and animal survival rate have shown succinasol advantages as compared to the lactate-saline blood substitute in acute massive hemorrhage and reversible hemorrhagic shock.

Animals↗

Fluid resuscitation after an otherwise fatal hemorrhage: I. Crystalloid solutions.

One half of deaths among trauma victims occur within 1 hour of injury and are due to rapid hemorrhage or CNS trauma. We developed a rapid hemorrhage model in unanesthetized swine to simulate human exsanguination. We compared the ability of four crystalloid solutions to prevent death after an otherwise fatal hemorrhage: normal saline (NS), Ringer's lactate (RL), Plasmalyte-A (PA), and Plasmalyte-R (PR). Five days before hemorrhage swine received an aortic sideport and a central venous treatment catheter. Aortic blood (54 ml/kg) was removed in 15 minutes from 116 swine. The percentages of shed blood replaced were 14% in 5 minutes with NS, 100% in 20 minutes with NS, and 300% in 30 minutes with NS, RL, PA, or PR. We found that all mortalities were determined within 2 hours after hemorrhage and that RL provided the best survival rate of 67% (NS 300% = 50%, PR = 40%, and PA = 30%.) After an analysis of arterial blood gas, lactate, acid-base, heart rate, and aortic pressure measurements, we conclude that RL is the superior crystalloid solution because of its decreased chloride load (compared to NS) and because of the absence of acetate or magnesium (compared to PA and PR).

Acid-Base Equilibrium↗

Urinary indices of horses after intravenous administration of crystalloid solutions.

Saline or glucose solution was infused for approximately 4 hours into six healthy mares in two separate experiments to determine the effect of infusion of crystalloid solutions on fractional excretion (FE) of sodium (Na), chloride (Cl), potassium (K), and phosphorus (P), ratio of urinary creatinine to serum creatinine (UCr/SCr), and ratio of urinary osmolality to serum osmolality (Uosm/Sosm). After intravenous infusion of either saline or glucose solution, FENa, FECl and FEP were significantly increased, whereas UCr/SCr and Uosm/Sosm were significantly decreased. In addition, FEK was significantly increased after infusion of glucose solution. It was concluded that urinary indices were altered by intravenous infusion of crystalloid solutions in healthy mares and that fluid therapy may interfere with the use of these indices for diagnostic purposes.

Animals↗

Effects of colloid or crystalloid solutions on edemagenesis in normal and thrombomicroembolized lungs.

We studied the effects of crystalloid (75 ml/kg of Ringer's lactate) or colloid (6% dextran-70, 6% hydroxyethyl starch, or 25 ml/kg of 5% human serum albumin) fluid infusions or no treatment (control) on the calculated lung capillary (Pc)-plasma oncotic pressure (pi c) gradient and pulmonary edema. Two sets of mongrel dogs were studied: uninjured (n = 25; 14 to 22 kg) and pulmonary fibrin-microembolized (n = 25; 15 to 23 kg). In both sets of experiments, left atrial pressure was controlled (15 mm Hg) throughout the 4-h plus experimental period. In the uninjured set, the Pc-pi c gradient averaged +1.0 and -0.2 mm Hg in the hydroxyethyl starch and dextran groups, +0.7 and +2.3 mm Hg in the human serum albumin and control groups, and +6.2 mm Hg in the Ringer's lactate group. In the fibrin-microembolized group, this gradient averaged 2.6, 2.4, 3.0, 5.3, and 9.5, respectively. The extravascular lung water to bloodless dry lung wet weight ratios in the no-fluid treatment group of the uninjured and microembolism groups with increased pressure (3.8 +/- 0.3 to 4.1 +/- 0.4 [SEM]; NS) are consistent with interstitial or perivascular edema. There were, however, no significant differences noted between the respective control groups or any fluid treatment group in either set of experiments. These data support the view that infusion of either colloid or crystalloid solutions in normal or pulmonary fibrin-microembolized lungs does not produce sufficient change in the Pc-pi c gradient to elevate edemagenesis when pulmonary capillary pressure is limited to 22 mm Hg in dogs.

Animals↗

Haemodynamic, acid-base and electrolyte changes during plasma replacement with hydroxyethyl starch or crystalloid solution in young pigs.

We investigated haemodynamic, acid-base and electrolyte changes during almost total plasma replacement with hydroxyethyl starch (HES) and physiological balanced electrolyte solution (PBE) by using a cell saver in ten young pigs. In the PBE group an additional 3550 (444) ml crystalloid solution [Mean (SD)] was infused over the course of the study in order to maintain pulmonary capillary wedge pressure. Plasma protein levels decreased in both groups and the colloid osmotic pressure increased in HES and decreased in PBE. At the end of the study, body weight [HES 10.4 (1), PBE 13.1 (1.4) kg, P < 0.01] and lactic acid concentration [HES 0.9 (0.3), PBE 2.9 (1. 3) mmol.l -1, P < 0.01] was higher and tissue oxygen delivery [HES 327 (22), PBE 89 (29) ml.min.m2, P < 0.01] was lower in the PBE group. There were only moderate acid-base changes in both groups, but at the end, anion gap was significant lower in HES. In conclusion, maintenance of colloid osmotic pressure close to the physiological range of infants seems to be advantageous during major paediatric surgery.

Acid-Base Equilibrium↗

Small-volume resuscitation. Crystalloid solutions for intravascular volume replacement.

There is growing interest in the use of hypertonic crystalloid solutions for intravascular volume replacement. Such solutions rapidly restore nutrient blood flow to vital organs by a combination of increased perfusion pressure and vascular dilation. The addition of colloid to the solution appears to improve survival by limiting the tissue damage caused by ischemic injury and may avert the development of multisystem organ failure. Low cost and long shelf life make hypertonic solutions attractive for acute resuscitation after major trauma, but further investigations are warranted as to their efficacy and safety in the clinical setting.

Animals↗

Improved preservation of coronary endothelial function with Celsior compared with blood and crystalloid solutions in heart transplantation.

BACKGROUND: Endothelial injury from preservation solutions has been implicated in acute coronary vasospasm and pathologic activation of the endothelium, which can contribute to the development of graft coronary vasculopathy after heart transplantation. Preservation solutions with a powerful antioxidant capacity may decrease the occurrence of these complications. MATERIALS AND METHODS: This study was designed to evaluate the effect of Celsior (an anti-oxidant solution specifically designed for cardiac preservation) in a model of heart preservation (4 hours at 4 degrees C to reproduce the situation encountered in clinical heart transplantation) compared two commonly used cardioplegic and preservation strategies on coronary endothelial function. Endothelium-dependent relaxation of normal porcine epicardial coronary arteries to serotonin (5-HT, an agonist that activates 5-HT(1d) receptors coupled to Gi proteins) and bradykinin (BK, which activates B2 receptors coupled to Gq proteins) was studied in standard organ chamber experiments in the following groups: a control group was submitted to immediate excision without cardioplegia and preserved in saline solution (0.9% NaCl) for 4 hours (Group 1); two groups had cardioplegia induced with a crystalloid solution and were stored for 4 hours in saline (Group 2) or 4 hours in Celsior solution (Group 3); and two groups had cardioplegia induced with normothermic blood cardioplegia and were stored for 4 hours in the saline (Group 4), or 4 hours in Celsior solution (Group 5). Finally, two groups underwent cardioplegia with Celsior and were stored for 4 hours in saline (Group 6), or 4 hours in the Celsior solution (Group 7). All cardioplegia solutions were at 4 degrees C (except blood cardioplegia at 37 degrees C) and all preservations solutions were at 4 degrees C. RESULTS: Endothelium-dependent relaxations to serotonin were significantly decreased in all groups except the Celsior + Celsior group compared with the control group. There were no significant differences in relaxation to bradykinin except in one group. Use of the Celsior solution for induction of cardioplegia and storage better preserved endothelium-dependent G-protein-mediated relaxation compared with the other arrest and preservation strategies. CONCLUSIONS: The observed effect may be associated with an improvement in both short- and long-term outcome in heart transplantation, especially because these alterations may be further compounded by reperfusion.

Animals↗

Expansion of extracellular tracer spaces in the isolated heart perfused with crystalloid solutions: expansion of extracellular space, trans-sarcolemmal leakage, or both?

Comparisons of the distributions of tracers putatively confined to the myocardial extracellular space (ECS) in vivo and in isolated hearts perfused with crystalloid solutions via their coronaries, generally indicate that ECS markedly expands--both absolutely and relative to cellular space (ICS)--over a period of in vitro perfusion. Quantification of the expansion is problematic, however, because of the difficulty of distinguishing between a true increase in anatomical ECS and expansion of tracer space due to penetration of the plasma membrane. This difficulty in turn renders an assessment of the distribution of electrolytes and other substances unreliable. In the present study a combined morphometric-tracer distribution analysis is applied towards distinguishing between ECS expansion and tracer leakage in the rat Langendorff preparation perfused with a modified Krebs-Henseleit solution. The results demonstrate that both ICS and ECS expanded with the first few minutes of perfusion, with the ICS remaining constant thereafter and the ECS increment declining slowly. Although the expansion of the ECS initially is disproportionately greater relative to that of the ICS, this relative difference disappears in about 1 h, i.e., the uptake of water by the myocardium is nearly homogeneous. An apparent increase of ECS relative to ICS, by more than one-third the initial space after 90 min perfusion, was found to be entirely artifactual and apparently due to a non-specific increase in sarcolemmal permeability.

Animals↗