Findings of a hospital surveillance-based outcome evaluation study for Clostridium difficile-associated colitis.

We completed a prospective study of 164 patients involved in a Clostridium difficile surveillance programme, evaluating a range of variables such as disease severity, treatment regimen and known clinical risk factors, for their effect on case lethality. The aim of this study was to determine if there are any additional clinical variables worth considering for inclusion in the therapeutic decision-making process. Beyond common risk factors, secondary immunodeficiencies such as diabetes mellitus, malignancy, autoimmune disease, immunosuppressive therapy and chronic hepatitis were assessed. Overall case lethality was 23%. There was a suggestion that regular proton pump inhibitor use in past medical history might be associated with greater lethality. Immunosuppressive therapy within 1 month before the onset of diarrhoea was associated with a significant four-fold lethality increase. This last finding may have the potential to further improve therapeutic judgement if used as an explicit component of a revised scoring system. In relation to Clostridium difficile-associated colitis, immunosuppressive therapy as a red flag entity, as described here, has not been previously published.

Changes of PACAP levels in the brain show gender differences following short-term water and food deprivation.

Pituitary adenylate cyclase activating polypeptide (PACAP) is a pleiotropic neuropeptide exerting diverse actions in the central and peripheral nervous systems. A few studies indicate that PACAP is involved in the regulation of feeding and water homeostasis. The aim of the present study was to investigate changes in PACAP38 concentrations in different brain areas following food or water deprivation in male and female rats. Rats were sacrificed 12, 36 and 84h after water or food removal. PACAP levels were determined by radioimmunoassay. Our results show that levels of PACAP decreased in the hypothalamus in both sexes after water deprivation, with a more marked, significant decrease in females at 12h. A decrease was observed also in the telencephalon, with a similar pattern in both genders: levels were lowest after 12h, and showed a gradual increase at the other two time-points. PACAP levels increased in the brainstem of male rats, while females had a decrease 12h after water deprivation. The pattern of changes in PACAP levels was very different after food deprivation. In male rats, PACAP levels showed a significant increase in the hypothalamus, telencephalon and brainstem 12h after the beginning of starvation. In females, a less marked increase was observed only in the hypothalamus while no changes were found in the other brain areas. Our results show a sensitive reaction in changes of endogenous PACAP levels to water and food deprivation in most brain areas, but they are differentially regulated in male and female rats.

Vascular changes play a role in the pathogenesis of necrotizing enterocolitis in asphyxiated newborn pigs.

Necrotizing enterocolitis (NEC) is the most common acquired gastrointestinal emergency in neonates. We have developed an animal model of NEC in asphyxiated newborn pigs and investigated the effects of asphyxia on blood flow in superior mesenteric artery and abdominal aorta, cardiovascular data, arterial acid-base and blood gas parameters, and endothelial cytoskeletal structure in mesenteric microvasculature. Anesthetized, mechanically ventilated newborn pigs were included in two groups: piglets underwent severe asphyxia, and sham-operated control animals. A cardiovascular and metabolic failure developed in asphyxiated piglets approximately 1 h after the induction: severe hypotension and bradyarrhythmia were seen and significant reductions of the blood flow were measured in the superior mesenteric artery and abdominal aorta during the critical phase. Rearrangement of cytoskeletal actin structure corresponding to enhanced vascular permeability was seen with bodipy phallacidin in mesenterial endothelium of asphyxiated piglets after a 24-h recovery period. In conclusion, severe vasomotor changes during asphyxia may result in mesenteric endothelial dysfunction implicated in increased vascular permeability, edema formation, and development of NEC in asphyxiated piglets.

The effect of micronised fenofibrate on paraoxonase activity in patients with coronary heart disease.

OBJECTIVE: To evaluate the effect of micronised fenofibrate on serum paraoxonase (PON) and lipoprotein levels in coronary heart disease patients with type IIb hyperlipidemia. PATIENTS AND METHODS: Fifty-two patients were investigated for the three-month effect of 200 mg per day micronised fenofibrate on the serum enzyme activity and concentration of PON and their relationship with serum lipids, high-density lipoprotein (HDL-C) parameters. RESULTS: Serum paraoxonase activity was lower in CHD patients with type IIb hyperlipoproteinemia. During the three-month study it was observed that following treatment with micronised fenofibrate, serum triglyceride and cholesterol levels decreased, while HDL-C increased significantly (p<0.001). Low-density lipoprotein (p<0.05) and apolipoprotein B-100 (p<0.01) decreased, while HDL constituent apolipoprotein A-I (p<0.05) increased after micronised fenofibrate treatment. The HDL-associated paraoxonase specific activity increased significantly (p<0.05). To assess whether the increased PON activity was due to elevated HDL and apoA-I level, we standardized PON activity for HDL and apoA-I concentrations. The standardized values for HDL (PON/HDL) increased (p<0.05) while the PON/apoA-I ratio did not change significantly. CONCLUSION: Three months of treatment with micronised fenofibrate is thought to normalize lipid profile and improve antioxidant status by increasing serum paraoxonase activity in these patients.

Impairment by lovastatin of neural relaxation of the rabbit sphincter of Oddi.

We sought whether inhibition of cholesterol biosynthesis by lovastatin influenced the nitrergic relaxation response of the sphincter of Oddi. Rabbit sphincters of Oddi rings were tested for changes in isometric tension in response to field stimulation in the presence of 4 microM guanethidine and 1 microM atropine. Tissue samples were then analyzed for cAMP and cGMP content by radioimmunoassay for nitric oxide concentration by electron spin resonance and for vasoactive intestinal peptide and calcitonin gene-related peptide (CGRP) release by radioimmunoassay. Membrane G(salpha) protein was determined by Western blot analysis. Field stimulation relaxed the preparations with an increase in nitric oxide, cAMP and cGMP concentrations at increased calcitonin gene-related peptide and vasoactive intestinal polypeptide (VIP) release. Preparations from rabbits pre-treated with lovastatin (5 mg/kg/day intragastrically, over 5 days) contracted under the same conditions with an attenuated cGMP-increase at preserved increase in NO content and neuropeptide release. The relaxation was recaptured combining lovastatin with farnesol (1 mg/kg intravenously, twice a day for 5 days). The field stimulation-induced increase in cyclic nucleotides was also restored. Lovastatin decreased membrane G(salpha) protein content, which was re-normalized by farnesol. Farnesol treatment reinstates neurogenic relaxation of the sphincter of Oddi deteriorated by lovastatin possibly by normalizing G-protein coupling.

Deterioration of the protein kinase C-K(ATP) channel pathway in regulation of coronary flow in hypercholesterolaemic rabbits.

We studied the effect of experimental hypercholesterolaemia/atherosclerosis on changes in coronary flow and cardiac function, induced by protein kinase C and ATP-sensitive K(+) (K(ATP)) channel modulators in isolated Langendorff-perfused rabbit hearts. Both phorbol 12-myristate-13-acetate (PMA) and phorbol 12,13-dibutyrate (PDB, 0.1 microM each), activators of protein kinase C, decreased, whereas staurosporine, (0.1 microM), a protein kinase C inhibitor, increased coronary flow and left ventricular dP/dt, an index of ventricular contractility. Glyburide (5-50 microM), a K(ATP) channel inhibitor, blocked the effect of staurosporine. The phorbol esters were without effect in the presence of pinacidil (5 microM), a K(ATP) channel activator. Neither the protein kinase C modulators nor glyburide produced any effect on coronary flow and left ventricular contractility, when the hearts were prepared from animals either maintained on a cholesterol (1.5%)-enriched diet or treated with lovastatin (5 mg/kg/day per os). Treatment with farnesol (1 mg/kg twice a day for 7 days intravenously) restored the reactivity of hearts from either hypercholesterolaemic or lovastatin-treated animals to protein kinase C modulators. We conclude that non-cholesterol mevalonate products are necessary for the functional integrity of the protein kinase C-K(ATP) channel pathway in the rabbit heart.

Impaired bronchomotor responses to field stimulation in guinea-pigs with cisplatin-induced neuropathy.

Pre-treatment with cisplatin (3 mg/kg) i.p. once a day over 6 days induced sensory neuropathy as confirmed by femoral nerve conduction velocity test and significantly decreased contractions induced by electrical field stimulation (100 stimuli, 20 V, 0.1 ms, 20 Hz) in isolated main bronchial rings from guinea-pigs. The field stimulation-induced non-adrenergic, non-cholinergic (NANC) relaxations, however, were amplified in rings from animals with cisplatin neuropathy. The NANC relaxation response was completely blocked by 30 microM N(G)-nitro-L-arginine methyl ester in preparations from both control and cisplatin-treated animals. Superoxide dismutase (40 units/ml) was without effect on NANC relaxation in control rings, however, it substantially decreased NANC relaxation in preparations from animals with cisplatin neuropathy. These results show that cisplatin-induced sensory neuropathy is accompanied by attenuation of neural bronchoconstriction and an enhanced NANC relaxation. The latter is in part attained by an increased peripheral superoxide production.

Systemic anti-inflammatory effect of somatostatin released from capsaicin-sensitive vagal and sciatic sensory fibres of the rat and guinea-pig.

The systemic anti-inflammatory effect induced by antidromic sensory nerve stimulation was investigated in rats and guinea-pigs. In atropine-pretreated rats, bilateral antidromic stimulation of vagal afferent fibres (8 Hz, 20 min, at C-fibre strength) inhibited plasma extravasation induced by 1% mustard oil on the acutely denervated hindlegs by 36.45+/-3.95%. Both the prevention of this inhibitory effect by cysteamine pretreatment and the stimulation-evoked rise of plasma somatostatin-like immunoreactivity in the two species suggest a mediator role of neural somatostatin. Since this response was blocked by systemic capsaicin pretreatment and slightly reduced after subdiaphragmal vagotomy, participation of thoracic capsaicin-sensitive afferents is indicated. In guinea-pigs pretreated with guanethidine and pipecuronium, antidromic sciatic nerve stimulation induced 45.46+/-5.08% inhibition on the contralateral leg and increased plasma somatostatin-like immunoreactivity. It is concluded that somatostatin released from the activated vagal capsaicin-sensitive sensory nerve terminals of the rat and somatic nerves of the guinea-pigs exerts a systemic humoral function.

Direct myocardial anti-ischaemic effect of GTN in both nitrate-tolerant and nontolerant rats: a cyclic GMP-independent activation of KATP.

1. We have recently demonstrated that glyceryl trinitrate (GTN) exerts a direct myocardial anti-ischaemic effect in both GTN-tolerant and nontolerant rats. Here we examined if this effect is mediated by GTN-derived nitric oxide (NO) and involves guanosine 3'5' cyclic monophosphate (cyclic GMP) and ATP-sensitive K+ channels (KATP). 2. Rats were treated with 100 mg kg-1 GTN or vehicle s.c. three times a day for 3 days to induce vascular GTN-tolerance or nontolerance. Isolated working hearts obtained from either GTN-tolerant or nontolerant rats were subjected to 10 min coronary occlusion in the presence of 10-7 M GTN or its solvent. 3. GTN improved myocardial function and reduced lactate dehydrogenase (LDH) release during coronary occlusion in both GTN-tolerant and nontolerant hearts. 4. Cardiac NO content significantly increased after GTN administration in both GTN-tolerant and nontolerant hearts as assessed by electron spin resonance. However, cardiac cyclic GMP content measured by radioimmunoassay was not changed by GTN administration. 5. When hearts from both GTN-tolerant and nontolerant rats were subjected to coronary occlusion in the presence of the KATP-blocker glibenclamide (10-7 M), the drug itself did not affect myocardial function and LDH release, however, it abolished the anti-ischaemic effect of GTN. 6. We conclude that GTN opens KATP via a cyclic GMP-independent mechanism, thereby leading to an anti-ischaemic effect in the heart in both GTN-tolerant and nontolerant rats.

Rapid pacing-induced preconditioning is recaptured by farnesol treatment in hearts of cholesterol-fed rats: role of polyprenyl derivatives and nitric oxide.

We have previously shown that hypercholesterolemia leads to the loss of pacing-induced preconditioning (PC), possibly due to the impairment of cardiac nitric oxide (NO) synthesis. It has been shown that excess exogenous cholesterol inhibits formation of several polyprenyl derivatives involved in signal transduction. In the present study, we examined whether PC and cardiac NO synthesis are restored by treatment with the key polyprenyl product, farnesol, in cholesterol-fed rats. Rats fed 2% cholesterol-enriched/control diet for 24 weeks were given i.p. 5 microM/kg farnesol/vehicle, respectively. An hour later, hearts were isolated and prepared for 'working' perfusion, then subjected to PC/non-PC protocols of 3 intermittent periods of pacing of 5 min duration at 10 Hz, followed by a 10 min coronary occlusion to test the effect of PC. PC increased ischemic aortic flow (AF) from its control value of 15.6+/-1.5 to 27.3+/-1.7 mL/min (p < 0.05). PC was not observed in hearts obtained from hypercholesterolemic rats (AF: 15.7+/-1.2 mL/min), however, it reappeared in the farnesol-treated hypercholesterolemic group (AF: 31.8+/-3.4 mL/ min, p < 0.05). In tissue samples from the left ventricle, cholesterol-diet markedly decreased the intensity of the electron spin resonance spectra of NO obtained after in vivo spin trapping with Fe2+-diethyl-dithio-carbamate complex. Farnesol-treatment did not influence cardiac NO content in the cholesterol-fed or in the control group. These results show that the lost PC can be recaptured by farnesol-treatment in hypercholesterolemia, however, farnesol-treatment does not restore cardiac NO synthesis.

Cross tolerance between nitroglycerin and neural relaxation of the rabbit sphincter of Oddi.

We studied whether non-adrenergic, non-cholinergic (NANC) relaxation of the rabbit sphincter of Oddi was influenced by tolerance to nitroglycerin (NG) in vitro. Sphincter of Oddi (SO) muscle rings precontracted with EC50 concentrations of cholecystokinin octapeptide (CCK8) were exposed to cumulative increases in NG concentrations and tested for relaxation by measurement of isometric tension. A separate group of six rings was subjected to a preceding exposure to 275 microM nitroglycerin over 60 min to induce in vitro tolerance to nitroglycerin. The rings (both tolerant and non-tolerant) were subjected to electrical field stimulation (FS: 50 V, 0.1 ms, 20 Hz, 3 and 10 stimuli). The rings were then preincubated with NANC solution: phentolamine, oxprenolol and atropine (all 1 microM) for 20 min and FS was applied again. FS was repeated after additional incubation with NG-nitro-L-arginine methyl ester (L-NAME), and inhibitor of NO synthase (30 microM) and after a successive incubation with 3 mM L-arginine (20 min). Maximum contractions produced by CCK8 in 'tolerant' and 'non-tolerant' sphincters were 29.9 +/- 5.8 and 28.3 +/- 5.2 mN, respectively. The sensitivity to CCK8 also was not different between the two groups with EC50 (-log M) values of 8.5 +/- 0.2 and 8.3 +/- 0.1, respectively. FS evoked twitchlike contraction followed by relaxation in the ampullary SO in both 'tolerant' and 'non-tolerant' preparations. Incubation in NANC solution resulted in monophasic relaxations in response to FS in non-tolerant sphincters but not in tolerant ones. L-NAME (30 microM) reversed NANC relaxation in non-tolerant muscle rings whereas it failed to modify NANC contractions in the tolerant preparations. L-arginine (3 mM) reversed the inhibitory effect of L-NAME on NANC relaxation in the 'non-tolerant' rings and it was without effect on FS-induced contractions in the 'tolerant' SO. As measured by radioimmunoassay, tolerance to NG was without any significant effect on tissue content of both cyclic adenosine 3':5' monophosphate (cAMP) and cyclic guanosine 3':5' monophosphate (cGMP). FS significantly increased tissue cAMP and cGMP content in 'non-tolerant' preparations. FS failed to increase the level of either cyclic nucleotide in 'tolerant' tissue. We conclude that NANC relaxation of the ampullary part of the rabbit SO is significantly impaired in the state of tolerance to NG 'in vitro'.

Cochlear implantation of a Hungarian deaf and blind patient with discharging ears suffering from Behçet's disease.

A case is reported in which a Nucleus 22 channel intracochlear device was implanted a deaf/blind Hungarian adult with discharging ears suffering from Behçet's disease. Preconditioning surgery was employed three months prior to the implantation procedure to ensure a sterile, dry protected environment for the electrodes. One month after implantation, the patient exhibited excellent auditory discrimination capability at the time of the first switch on. We suggest that some deaf/blind individuals may serve as very good candidates for intracochlear implantation.

Glibenclamide sensitivity of neural relaxation of the rabbit sphincter of oddi.

In this article we studied whether the nitrergic relaxation of the rabbit sphincter was sensitive to glibenclamide. Field stimulation relaxed the sphincter of Oddi rings after incubation with atropine (1 microM) and guanethidine (4 microM) with threefold and fourfold increases in tissue guanosine 3':5'-cyclic monophosphate and adenosine 3':5'-cyclic monophosphate contents, respectively. These changes were blocked by 30 microM NG-nitro-L-arginine methyl ester. Glibenclamide (0.1-10 microM) attenuated the field stimulation-induced relaxation and completely abolished the relaxation produced by 0.1 microM cromakalim. We conclude that nitrergic relaxation of the rabbit sphincter of Oddi comprises a mechanism sensitive to glibenclamide.

The effect of continuous versus intermittent treatment with transdermal nitroglycerin on pacing-induced preconditioning in conscious rabbits.

1. Tolerance to the hypotensive effect of nitroglycerin (NG) blocks preconditioning induced by rapid ventricular pacing (RVP) in rabbits. In the present work the effect of continuous versus intermittent treatment with transdermal nitroglycerin on the pacing-induced preconditioning phenomenon was studied in conscious rabbits. 2. RVP (500 beats min-1 over 5 min) increased left ventricular end-diastolic pressure (LVEDP) from baseline 4.1 +/- 0.9 to postpacing 13.8 +/- 2.9 mmHg (P < 0.001) with a right intraventricular ST-segment elevation of 1.25 +/- 0.13 mV, two indicators of myocardial ischaemia. These changes were significantly attenuated when the RVP period was preceded by a preconditioning pacing of the same rate and duration with an interpacing interval of 5 min. 3. Protection by preconditioning was abolished when the animals had been made tolerant to the vasodilator effect of 30 micrograms kg-1 NG by the application of transdermal NG (approx. 0.07 mg kg-1 h-1) over 7 days. Furthermore, transdermal NG per se attenuated both RVP-induced ST-segment elevation and LVEDP-increase over the 7 day period. 4. With intermittent transdermal NG treatment (12 h 'patch on' vs 'patch off'), neither development of vascular tolerance nor attenuation of the NG- or preconditioning-induced anti-ischaemic effects were observed. However, the severity of pacing-induced myocardial ischaemia was significantly increased during the 'patch off' periods. 5. In a second set of experiments, postpacing changes in cardiac cyclic GMP and cyclic AMP levels were determined by means of radioimmunoassay in chronically instrumented anaesthetized open-chest rabbits with the same NG-treatment protocols. Preconditioning reduced postpacing increase in cyclic AMP with an increase in cyclic GMP concentrations in hearts of the untreated animals and in those given patches intermittently during both 'patch on' and 'patch off' periods. However, the preconditioning effect on either cyclic nucleotide was blocked in the tolerant animals. 6. Transdermal NG increased resting levels of both cardiac cyclic nucleotides in the non-tolerant but not in the tolerant state. The postpacing increase in cyclic AMP content was inhibited by transdermal NG, independent of vascular tolerance development, whereas an cyclic GMP content was exclusively seen in the non-tolerant animals. 7. We conclude that the anti-ischaemic effect of NG is independent of the cyclic GMP mechanism in the tolerant state. While intermittent NG therapy prevents development of vascular tolerance and preserves preconditioning, the nitrate-free periods yield an increased susceptibility of the heart to ischaemic challenges.

Ventricular overdrive pacing-induced anti-ischemic effect: a conscious rabbit model of preconditioning.

To study whether ventricular overdrive pacing (VOP) induces preconditioning, rabbits were equipped with right ventricular electrode catheters for pacing and intracavital recording and polyethylene cannulas in the left ventricle and right carotid artery to measure intraventricular pressure and blood pressure. One week after surgery in conscious animals, VOP at 500 beats/min over 2, 5, or 10 min resulted in an intracavital S-T segment elevation, shortening of ventricular effective refractory period, decrease in maximum rate of pressure development and blood pressure, and increase in left ventricular end-diastolic pressure proportional to the duration of stimulation. A 5-min preconditioning VOP applied 5 or 30 min before a 10-min VOP markedly attenuated ischemic changes, whereas a 2-min VOP had no effect. In anesthetized rabbits, a 5-min VOP slightly increased guanosine 3',5'-cyclic monophosphate (cGMP) and profoundly elevated adenosine 3',5'-cyclic monophosphate (cAMP) content in left ventricular samples. When this VOP was preceded (5 or 30 min) by a preconditioning VOP, the cAMP increase was significantly attenuated, whereas the cGMP increase was amplified. We conclude that a single 5-min VOP induces preconditioning in association with alterations in cardiac cyclic nucleotide contents.

Cicletanine attenuates overdrive pacing-induced global myocardial ischemia in rabbits: possible role of cardiac cyclic nucleotides.

BACKGROUND: This study examined whether cicletanine, an antihypertensive drug with cGMP phosphodiesterase inhibitory effect, could alleviate ventricular overdrive pacing-induced myocardial ischemia in chronically instrumented rabbits. METHODS: An electrode-catheter implanted into the right ventricle was used for pacing (500 bpm over 5 min) and for measuring intracavital ST-segment elevation and ventricular effective refractory period (VERP). PQ and QT intervals were measured in the chest-lead ECG, and dP/dtmax as well as left ventricular end-diastolic pressure (LVEDP) were recorded through a left intraventricular catheter. In separate groups, mean arterial blood pressure (MABP) was monitored from the right carotid artery. Experiments were performed on conscious rabbits after a week of convalescence. In anesthetized, open-chest rabbits, samples were taken from the left ventricle before and after drug treatment and/or overdrive pacing for determination of cGMP and cAMP contents by radioimmunoassay. RESULTS: Intravenous cicletanine, 30 mg/kg body weight, did not change resting MABP, dP/dtmax, and LVEDP, but it did reduce heart rate and prolonged PQ and QT intervals and VERP. Overdrive pacing produced intracavital ST-segment elevation, increased LVEDP, and decreased dP/dtmax and MABP. Cicletanine administered 15 minutes before pacing significantly attenuated ST-segment elevation, increased LVEDP, and decreased dP/dtmax and MABP. In anesthetized animals, cicletanine itself slightly increased cardiac cGMP and cAMP contents. Overdrive pacing moderately increased cGMP and profoundly elevated cAMP, and in overpaced rabbits, cicletanine further increased cGMO and markedly attenuated cAMP content increased by overdrive pacing. CONCLUSIONS: These results suggest that in correlation with alterations of cardiac cycle nucleotide contents, cicletanine protects the heart against pacing-induced myocardial ischemia.

Cardioprotection: endogenous protective mechanisms promoted by prostacyclin.

Evidence is accumulating that acute stress situations such as ischemia, adrenergic dominance, and ouabain intoxication enhance production of endogenous substances (PgI2, adenosine, NO) which may protect the myocardium from harmful consequences of these stress situations. PgI2 and its stable analogue 7-oxo-PgI2 exert an early direct- and induce a delayed indirect antiischemic, antiarrhythmic, and cytoprotective effect. The direct action is shortlasting; it protects from myocardial ischemia and arrhythmias, at least partly, by its vasodilating, antiaggregatory, and "membrane-stabilizing" effects. The delayed, long-lasting PgI2-induced protection from postocclusion, reperfusion- and ouabain-arrhythmias is dose- (optimal 50 micrograms/kg) and time- (optimal 48 h after treatment) dependent. Its mechanism is probably based on a 7-oxo-PgI2 induced increase in the activity of Na/K-ATP-ase, and further, on a reduced sensitivity to beta-adrenergic agonists and to changes at the cardiac membrane level, resulting in a prolongation of the action potential duration and the effective refractory period.

On the nature and molecular basis of prostacyclin induced late cardiac changes.

The late appearing and long-lasting cardiac effects induced by PgI2 or its stable analogue 7-oxo-PgI2 described by us first in 1983 include: 1.) antiischemic, 2.) antiarrhythmic, 3.) selective electrophysiological and 4.) cardiac cytoprotective changes. Evidence for 1.: Protection from myocardial ischemia due to coronary occlusion in dogs furthermore a significant diminution of ischemic loss of the myocardial ATP and CP content and of the myocardial lactate accumulation in excised rat heart exposed to global ischemia. 2: Protection from postocclusion and reperfusion arrhythmias in dogs. 3: A selective prolongation of the ventricular refractory period (VERP) as well as of the action potential duration (APD90) in the isolated rabbit papillary muscle furthermore prolongation of QT distance and VERP in the rabbit and the guinea pig heart "in situ". 4.: The cardiac cytoprotective effect, i.e. ischemic loss of intracellular K+ and ischemic gain of intracellular Na+ in isolated hearts of 7-oxo-PgI2 treated guinea pigs subjected to 25 min global ischemia was significantly moderated. These protective actions proved to be dose and time dependent - maximal effects appeared 48 hrs after administration of a single dose of 50 micrograms/kg i.m. 7-oxo-PgI2. These effects are certainly not due to 7-oxo-PgI2 itself but this latter seems to be indispensable for induction of a long acting principle, which can probably be extracted from hearts of pretreated animals and this substance of lipoid character exerts electrophysiological effects similar to those observed after 7-oxo-PgI2 pretreatment. Pretreatment may also reduce isoproterenol induced heart rate increase and prolong bleeding time in conscious rabbits.(ABSTRACT TRUNCATED AT 250 WORDS)