Ventricular bigeminy associated with myocardial ischemia in a dog with a colonic torsion: a case report.

BACKGROUND: Ventricular bigeminy due to myocardial ischemia has been reported in humans as well as in canine patients with obstructive gastrointestinal diseases. This is the first case report of ventricular bigeminy in a dog with a colonic torsion that resolved after fluid resuscitation and restoration of myocardial perfusion. CASE PRESENTATION: An 11-year-old, male neutered mixed breed dog presented with a one day history of vomiting, tenesmus, and lethargy. Physical examination identified an irregular heart rhythm and intermittent pulse deficits. A ventricular arrhythmia represented by ventricular premature complexes (VPCs) organized in bigeminy, was appreciated on a 3-lead electrocardiogram (ECG) with a single lead (II) view. Abdominal radiographs confirmed a colonic torsion. Prior to anesthetic induction, ventricular bigeminy was non responsive to fentanyl or lidocaine. The patient was anesthetized and intravascular volume deficit was identified by dampened plethysmographic wave amplitude (plethysomographic variability), audible softening of the Doppler sound, and more pronounced pulse deficits. Fluid resuscitation was achieved with a combination of intravenous crystalloid and colloid fluid therapy comprising 7.2% hypertonic saline and 6% hetastarch. The patient's cardiac rhythm converted to normal sinus after fluid resuscitation. The colonic torsion was surgically corrected. The patient recovered well from anesthesia and was ultimately discharged from the hospital 5 days later. CONCLUSIONS: The present case report highlights that myocardial ischemia can lead to ventricular arrythmias, such as ventricular bigeminy. This is the first documented case of ventricular bigeminy in the canine patient with a colonic torsion. Assessment of patient volume status and appropriate fluid resuscitation along with continuous electrocardiogram (ECG) monitoring are vital to patient stability under general anesthesia.

Utility of cardiac MRI to diagnose myocardial ischemia and fibrosis in dogs with cardiomegaly secondary to myxomatous mitral valve disease.

OBJECTIVE: To assess whether cardiac MRI or various biomarkers can be used to detect myocardial ischemia and fibrosis in dogs with cardiomegaly secondary to myxomatous mitral valve disease (MMVD). ANIMALS: 6 dogs with cardiomegaly secondary to naturally occurring stage B2 MMVD being treated only with pimobendan with or without enalapril and 6 control dogs with no cardiac disease. All dogs were ≥ 5 years old with no systemic illness. PROCEDURES: Serum cardiac troponin I and concentrations were measured, and dogs were anesthetized for cardiac MRI with ECG-triggered acquisition of native T1- and T2-weighted images. Gadolinium contrast was administered to evaluate myocardial perfusion and late gadolinium enhancement (LGE). Mean T1 and T2 values and regions of LGE were measured with dedicated software. Extracellular volume (ECV) was estimated on the basis of Hct and T1 values of myocardium and surrounding blood. Subjective analysis for myocardial perfusion deficits was performed. RESULTS: Dogs with MMVD had significantly (P = .013) higher cardiac troponin I concentrations than control dogs, but galectin-3 concentrations did not differ (P = .08) between groups. Myocardial fibrosis was detected in 4 dogs with MMVD and 3 control dogs; no dogs had obvious myocardial perfusion deficits. Native T1 and T2 values, postcontrast T1 values, and ECV values were not significantly different between groups (all P > .3). CLINICAL RELEVANCE: Results suggest that some dogs with cardiomegaly secondary to MMVD may not have clinically relevant myocardial fibrosis.

Findings suggestive of coronary microvascular dysfunction in cats with myocardial ischemia.

Background: Myocardial infarction (MI) is an important cause of death and disability among humans worldwide. Few studies have reported the occurrence of MI in small animals as well. Reports in human medicine indicate that up to 30% of patients with clinical signs compatible with myocardial ischemia suggestive of coronary disease exhibit normal epicardial arteries at angiography. These symptoms have been associated with a syndrome characterized by alterations in cardiac microvasculature, known as coronary microvascular dysfunction (CMD). Aim: This study aimed to describe the necropsy findings and clinical-pathological characterization (when available) of cats with histopathological findings suggesting CMD. Methods: Necropsy records of cats presenting histopathological diagnosis compatible with acute and/or chronic MI, with normal epicardial arteries and microvascular disorders were evaluated. Results: Twenty animals met the inclusion criteria. Eight cats (40%) exhibited findings compatible with mild hypertrophic cardiomyopathy (HCM) without left atrial enlargement, one (5%) presented restrictive cardiomyopathy, and another one (5%) had lesions consistent with histiocytoid cardiomyopathy. The remaining cats (50%) showed alterations compatible with severe HCM with left atrial enlargement. In all cases, epicardial arteries were normal (without obstruction). All the evaluated hearts exhibited myocardial multifocal fibrosis along with replacement of cardiomyocytes by adipose tissue and blood vessels with hyperplasia and hypertrophy of the muscular layer with protrusion of the nuclei of the endothelial cells. Conclusion: These findings suggest the presence of microvascular dysplasia of the coronary arteries. Further studies are necessary to confirm and clinically characterize these results.

Sudden cardiac death: A comparative review of humans, dogs and cats.

Sudden death is one of the most common causes of death in humans in Western countries. Approximately 85% of these cases are of cardiac origin. In dogs and cats, sudden cardiac death (SCD) also commonly occurs, but fewer pathophysiological and prevalence data are available. Both structural, primarily 'electrical' and ischemic heart diseases are known to cause SCD, many of which share similar underlying arrhythmogenic mechanisms between humans and companion animals. As for underlying genetics, numerous mutations on multiple loci have been related to SCD in humans, but only a few mutations associated with dilated cardiomyopathy and SCD have been identified in dogs, e.g. in the phospholamban and titin genes. Information published from human medicine can therefore inform future veterinary studies, but also dogs and cats could act as spontaneous models of SCD in humans. Further research in both fields is therefore warranted to better understand the pathophysiology, genetics, and prevention of SCD.

Interventionist videothermometry: a new model of cardiac ischemia evaluation.

BACKGROUND: The purpose of the present study was to evaluate, through videothermometry, the temperature variation in the hearts of rabbits, that underwent induced myocardial ischemia and reperfusion. RESULTS: A total of 20 female rabbits were divided into two groups: a treated group and a sham group, the treatment group underwent 5 min of cardiac arrest and reperfusion, using the inflow occlusion technique. Throughout the experiment, the animals were monitored by videothermometry, observing the thermal variations of the myocardial tissue. During the experiment, at different times, blood gas tests and tests to evaluate the lactate concentrations were performed. At the end of the experiment, each heart was submitted to histopathological evaluation. In the treated group, there was a reduction in temperature of the myocardial tissue during the circulatory arrest compared to the sham group. Additionally, a colder area next to the caudal vena cava ostium and the right atrium was observed. Notably, despite the 5 min of cardiac arrest in the treated group, both the lactate and bicarbonate levels were maintained without significant variation. However, there was an increase in PaCO2 and pH reduction, featuring respiratory acidosis. In relation to the histopathological study, the presence of hydropic degeneration in the myocardium of animals in the treated group was observed. CONCLUSIONS: Based on these results, the videothermometry was efficient in identifying the range of myocardial tissue temperature, suggesting that the first areas to suffer due to cardiac arrest were the caudal vena cava ostium and the right atrium. However, in regard to the angiographic coronary thermography, the study was not feasible due to the small size of the coronary. There was no variation between the groups regarding the presence of myocardial infarction, myocardial congestion, myocardial edema and myocardial hemorrhage.

Chronic Pressure Overload Induces Cardiac Hypertrophy and Fibrosis via Increases in SGLT1 and IL-18 Gene Expression in Mice.

Increased gene expression levels of sodium-glucose cotransporter 1 (SGLT1) are associated with hypertrophic and ischemic cardiomyopathy. However, it remains unclear whether chronic pressure overload increases SGLT1 expression, which in turn induces hypertrophic cardiomyopathy. We hypothesized that pressure overload could increase SGLT1 gene expression, leading to the development of hypertrophic cardiomyopathy.To create pressure overload-induced cardiomyopathy, transverse aortic constriction (TAC) was performed in SGLT1-deficient (SGLT1-/-) and wild-type (WT) mice. Six weeks after surgery, all mice were investigated. We observed a reduction of left ventricular fractional shortening and left ventricular dilatation in TAC-operated WT but not in TAC-operated SGLT1-/- mice. SGLT1, interleukin 18, connective tissue growth factor, and collagen type 1 gene expression levels were increased in TAC-operated WT mouse hearts compared with that of sham-operated WT mouse hearts. Moreover, heart/body weight ratio and ventricular interstitial fibrosis were increased in TAC-operated WT mice compared with that of sham-operated WT mice. Interestingly, these factors did not increase in TAC-operated SGLT1-/- mice compared with that of sham-operated WT and SGLT1-/- mice. Phenylephrine, an adrenergic α1 receptor agonist, caused cardiomyocyte hypertrophy in neonatal WT mouse hearts to a significantly larger extent than in neonatal SGLT1-/- mouse hearts.In conclusion, the results indicate that chronic pressure overload increases SGLT1 and IL-18 gene expressions, leading to the development of hypertrophic cardiomyopathy. These results make SGLT1 a potential candidate for the therapeutic target for hypertension-induced cardiomyopathy.

mRNA and protein expression of sarcKATP channel subunit Kir6.2 after exercise-induced myocardial injury in rats.

OBJECTIVE: To investigate the expression of kir6.2 subunit of the sarcKATP channel in exercise-induced myocardial injury and to elucidate the underlying mechanism of myocardial protection by sarcKATP channels. MATERIALS AND METHODS: Healthy male Sprague Dawley(SD) rats were divided into the Control (C) and the Exhaustive Exercise (EE) group. The one-time exhaustive exercise-induced myocardial injury model was established on a treadmill at a speed of 35 m/min. Alterations in myocardial ischemia and hypoxia were examined by hematoxylin-basic fuchsin-picric acid (HBFP) staining and the concentration of cardiac Troponin I (cTnl), a sensitive and specific marker for myocardial injury, was detected using immunochemiluminescence analysis. The mRNA expression level, localization, and protein expression of sarcKATP channel subunit kir6.2 were determined by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), immunofluorescence, and Western blot analysis, respectively. RESULTS: When compared to Group C, rats in Group EE demonstrated significantly increased areas of myocardial ischemia and hypoxia. Moreover, increased serum levels of cTnI were detected. Increased kir6.2 expression was found on the surface of cardiomyocytes and kir6.2 protein expression was also significantly increased. CONCLUSIONS: Exercise-induced myocardial injury did not result in noticeable alterations in kir6.2 mRNA expression. However, kir6.2 protein expression was significantly increased and resulted in increased numbers of sarcKATP channel openings in the myocardium, thereby further inhibiting exercise-induced myocardial injury.

MicroRNA-223-3p inhibits the angiogenesis of ischemic cardiac microvascular endothelial cells via affecting RPS6KB1/hif-1a signal pathway.

BACKGROUND: MicroRNAs (miRNAs) are a recently discovered class of posttranscriptional regulators of gene expression with critical functions in the angiogenesis and cardiovascular diseases; however, the details of miRNAs regulating mechanism of angiogenesis of ischemic cardiac microvascular endothelial cells (CMECs) are not yet reported. METHODS AND RESULTS: This study analyzes the changes of the dynamic expression of miRNAs during the process of angiogenesis of ischemic CMECs by applying miRNA chip and real-time PCR for the first time. Compared with normal CMECs, ischemic CMECs have a specific miRNAs expression profile, in which mir-223-3p has the most significant up-regulation, especially during the process of migration and proliferation, while the up-regulation is the most significant during migration, reaching 11.02 times. Rps6kb1 is identified as a potential direct and functional target of mir-223-3p by applying bioinformatic prediction, real-time PCR and Western blot. Pathway analysis report indicates Rps6kb1 regulates the angiogenesis by participating into hif-1a signal pathway. Further analysis reveals that both the gene and protein expression of the downstream molecules VEGF, MAPK, PI3K and Akt of Rps6kb1/hif-1a signal pathway decrease significantly during the process of migration and proliferation in the ischemic CMECs. Therefore, it is confirmed that mir-223-3p inhibits the angiogenesis of CMECs, at least partly, via intervening RPS6KB1/hif-1a signal pathway and affecting the process of migration and proliferation. CONCLUSION: This study elucidates the miRNA regulating law in the angiogenesis of CMECs; mir-223-3p inhibits the process of migration and proliferation of ischemic CMECs probably via affecting RPS6KB1/hif-1a signal pathway, which in turn suppresses the angiogenesis. It is highly possible that mir-223-3p becomes a novel intervention core target in the treatment of angiogenesis of ischemic heart diseases.

La distensión de la región isquémica predice una mayor inducibilidad de fibrilación ventricular tras la oclusión coronaria en el modelo porcino / Distension of the ischemic region predicts increased ventricular fibrillation inducibility following coronary occlusion in swine

Introducción y objetivos. La distensión de la región isquémica se ha relacionado con una mayor incidencia de arritmias ventriculares espontáneas tras la oclusión coronaria. Analizamos si la distensión isquémica regional predice una mayor inducibilidad de fibrilación ventricular tras la oclusión coronaria en cerdos. Métodos. En 18 cerdos anestesiados con tórax abierto, se ocluyó la descendente anterior durante 60 min. Se monitorizó la longitud segmentaria en la región isquémica mediante cristales ultrasónicos. Se realizó estimulación programada basal, y después continuamente entre 10 y 60 min tras la oclusión. Resultados. La oclusión coronaria indujo un rápido aumento en la longitud telediastólica en la región isquémica, que alcanzó el 109,4±0,9% de los valores basales a los 10 min (p<0,001). Se completaron 6,6±0,5 protocolos de estimulación, que indujeron 5,4±0,6 episodios de fibrilación ventricular entre 10 y 60 min tras la oclusión. Ni los valores séricos de potasio ni el tamaño del área isquémica se asociaron significativamente con la inducibilidad de fibrilación ventricular. Por el contrario, el aumento en la longitud telediastólica 10 min tras la oclusión coronaria se asoció directamente (r=0,67; p=0,002) con el número de episodios inducidos de fibrilación ventricular e inversamente (r=–0,55; p=0,018) con el número de extraestímulos necesarios para inducir la arritmia. Conclusiones. La distensión regional isquémica predice una mayor inducibilidad de fibrilación ventricular tras la oclusión coronaria. Estos resultados subrayan la influencia potencial de los factores mecánicos, que actúan no sólo sobre los desencadenantes, sino también sobre el sustrato, en la génesis de las arritmias ventriculares malignas durante la isquemia aguda (AU)

Introduction and objectives. Distension of the ischemic region has been related to an increased incidence of spontaneous ventricular arrhythmias following coronary occlusion. This study analyzed whether regional ischemic distension predicts increased ventricular fibrillation inducibility after coronary occlusion in swine. Methods. In 18 anesthetized, open-chest pigs, the left anterior descending coronary artery was ligated for 60min. Myocardial segment length in the ischemic region was monitored by means of ultrasonic crystals. Programmed stimulation was applied at baseline and then continuously between 10 and 60min after coronary occlusion. Results. Coronary occlusion induced a rapid increase in end-diastolic length in the ischemic region, which reached 109.4% (0.9%) of baseline values 10min after occlusion (P<.001). On average, 6.6 (0.5) stimulation protocols were completed and 5.4 (0.6) ventricular fibrillation episodes induced between 10 and 60min of coronary occlusion. Neither baseline serum potassium levels nor the size of the ischemic region were significantly related to ventricular fibrillation inducibility. In contrast, the increase in end-diastolic length 10min after coronary occlusion was associated directly (r=0.67; P=.002) with the number of induced ventricular fibrillation episodes and inversely (r=–0.55; P=.018) with the number of extrastimuli needed for ventricular fibrillation induction. Conclusions. Regional ischemic expansion predicts increased ventricular fibrillation inducibility following coronary occlusion. These results highlight the potential influence of mechanical factors, acting not only on the triggers but also on the substrate, in the genesis of malignant ventricular arrhythmias during acute ischemia (AU)

Development of a rat respiratory mask and its application in experimental chronic myocardial ischaemia.

In addressing the challenge of the low survival rates of rats with myocardial ischaemia, we developed a novel respiratory mask. We tested this mask on the rat model. We gave attention to several features of the mask: (1) shape, (2) size, (3) inlet, (4) outlet, (5) compatibility between rat head and the mask, (6) connection between mask and ventilator. We found certain features, especially to influence mask efficacy. These features include: mask shape, mask inlet and outlet, mask connection to the respiratory machine, mask mount on the rat head. We examined the rat mask in a model of chronic myocardial ischaemia; our model was the ligation of the coronary artery. The rats with the masks experienced an increase in survival by a factor of 50-90% compared with rats deprived of the masks. Towards the examination of myocardial ischaemia, our new mask may offer a platform replete with both efficiency and stability.

Myocardial injury-related changes in plasma NT-proBNP and ANP concentrations in a canine model of ischemic myocardial injury.

Serial changes in plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) and atrial natriuretic peptide (ANP) concentrations are unknown in dogs with myocardial injury. The time-course secretory responses between NT-proBNP and ANP or cardiac troponin-T (cTnT) related to myocardial infarction (MI) were investigated in this study. Six dogs were anaesthetised and the left anterior descending artery was ligated. A transient decrease in cardiac function was detected 1h after MI but returned to baseline levels within 7 days and remained so for 6 months. Echocardiographic examination revealed focal ventricular dyskinesis throughout the study. Six months following MI, the left atrium to aorta ratio increased significantly although the relative wall thickness decreased significantly from baseline. Significantly elevated plasma NT-proBNP and cTnT concentrations were detected 1 day after MI and these gradually decreased over 28 days to baseline levels without left ventricular pressure elevation. Plasma ANP was elevated significantly 6 months after MI. The NT-proBNP assay is a helpful diagnostic indicator for identifying asymptomatic acute and subacute myocardial injury whereas plasma ANP concentration mainly reflects atrial dilation.

Atherosclerosis and ischemic cardiomyopathy in a captive, adult red-tailed hawk (Buteo jamaicensis).

An adult, male, captive red-tailed hawk (Buteo jamaicensis) of at least 19 years of age presented in dorsal recumbency. The hawk was nonresponsive, and despite initial supportive care, died shortly after presentation. Gross postmortem revealed no abnormal findings. Histologic examination demonstrated atherosclerosis and ischemic cardiomyopathy. This is the first reported case of atherosclerosis in a red-tailed hawk.

Current status of cardiac MRI in small animals.

Cardiac magnetic resonance imaging (MRI) on small animals is possible but remains challenging and not well standardized. This publication aims to provide an overview of the current techniques, applications and challenges of cardiac MRI in small animals for researchers interested in moving into this field. Solutions have been developed to obtain a reliable cardiac trigger in both the rat and the mouse. Techniques to measure ventricular function and mass have been well validated and are used by several research groups. More advanced techniques like perfusion imaging, delayed enhancement or tag imaging are emerging. Regarding cardiac applications, not only coronary ischemic disease but several other pathologies or conditions including cardiopathies in transgenic animals have already benefited from these new developments. Therefore, cardiac MRI has a bright future for research in small animals.

Angiogenesis therapy with human tissue kallikrein for the treatment of ischemic diseases.

Angiogenesis is essential for the repair of wounds and tissues damaged by ischemia. The regenerative process is tightly regulated by master angiogenic factors, cytokines and the downstream mediator NO. In addition, modulators of vascular growth, such as COX-2-generated prostanoids, contribute to the process by stabilizing the hypoxia-inducible factor and stimulating the expression of VEGF. Recently, we discovered that human tissue kallikrein, a member of the serine proteinase superfamily, possesses potent angiogenic effects. It has been categorized as a pleiotropic angiogenic agent acting via enzymatic cleavage of kininogen and subsequent release of kinin peptides. Kinins bind G-protein coupled receptors, subtype B1 and B2, and exert proliferative effects on endothelial cells via an IP3K-Akt-NO mediated mechanism independent of VEGF. In addition, kinins stimulate the release of angiogenic prostacyclin. Gene transfer of human tissue kallikrein rescues ischemic tissues in otherwise normal mice, as well as in hypertensive or diabetic animals. In addition, prophylactic gene delivery of tissue kallikrein to diabetic skeletal muscles prevents the development of microangiopathy and stimulates collateralization, thus protecting from the consequences of supervening arterial occlusion.

Inhalation of concentrated ambient air particles exacerbates myocardial ischemia in conscious dogs.

Short-term increases in ambient air pollution have been associated with an increased incidence of acute cardiac events. We assessed the effect of inhalation exposure to concentrated ambient particles (CAPs) on myocardial ischemia in a canine model of coronary artery occlusion. Six mongrel dogs underwent thoracotomy for implantation of a vascular occluder around the left anterior descending coronary artery and tracheostomy to facilitate particulate exposure. After recovery (5-13 weeks), pairs of subjects were exposed for 6 hr/day on 3 or 4 consecutive days. Within each pair, one subject was randomly assigned to breathe CAPs on the second exposure day and filtered air at other times. The second subject breathed CAPs on the third exposure day and filtered air at other times. Immediately after each exposure, subjects underwent 5-min coronary artery occlusion. We determined ST-segment elevation, a measure of myocardial ischemia heart rate, and arrhythmia incidence during occlusion from continuous electrocardiograms. Exposure to CAPs (median, 285.7; range, 161.3-957.3 microg/m3) significantly (p = 0.007) enhanced occlusion-induced peak ST-segment elevation in precordial leads V4 (9.4 +/- 1.7 vs. 6.2 +/- 0.9 mm, CAPs vs. filtered air, respectively) and V5 (9.2 +/- 1.3 vs. 7.5 +/- 0.9 mm). ST-segment elevation was significantly correlated with the silicon concentration of the particles and other crustal elements possibly associated with urban street dust (p = 0.003 for Si). No associations were found with CAPs mass or number concentrations. Heart rate was not affected by CAPs exposure. These results suggest that exacerbation of myocardial ischemia during coronary artery occlusion may be an important mechanism of environmentally related acute cardiac events.

Mortality rates of interventional and surgical procedures performed in domestic juvenile farm pigs and Yucatan mini-pigs.

Perioperative and postoperative care are critical factors in cardiac catheterization and cardiothoracic surgical procedures. A retrospective analysis of mortality data in cardiovascular catheter and surgical studies performed in domestic juvenile swine (DJS) and Yucatan mini-swine (YMS) was conducted. A total of 529 animals in 35 studies were included in the analysis, which included six study categories: coronary stenting (Stent) and percutaneous transluminal coronary angioplasty (PTCA) alone; Stent and PTCA in combination with ionizing radiation (Stent/Rad, PTCA/Rad); myocardial ischemia (ISCH); and three non-ISCH surgical procedures grouped under "other surgeries" (Other Surg). Casualties were defined as animals that died spontaneously before the assigned termination date. The highest mortality rate occurred in the ISCH group (29.7% +/- 2.2%). Mortality of the Stent/Rad animals (26.1% +/- 6.3%) was significantly higher than those in the Stent and PTCA groups (12.1% +/- 3.1% and 7.9% +/- 3.2%; P< 0.05 for both). Similarly, mortality in the ISCH group was significantly higher than that in the Stent, PTCA, or Other Surg animals (29.7% +/- 2.2% versus 12.1% +/- 3.1%, 7.9% +/- 3.2%, and 3.0% +/- 3.0%, respectively; P< 0.05 for all comparisons). We did not observe differences between YMS and DJS. Most casualties in the ISCH group took place during weeks 1 (28.0% +/- 8.4%) and 4 (29.3% +/- 6.2%) after placement of the coronary ameroid constrictor. The majority of animals in the Stent/Rad and PTCA/Rad groups died within 1 week after the procedure (67.7% +/- 12.8% and 79.3% +/- 12.5%, respectively). We conclude that radiation therapy used in combination with stenting increases the mortality rate of this catheter-based procedure. Animals subjected to ISCH or a transcatheter procedure in combination with ionizing radiation should be monitored closely during the perioperative period to prevent unacceptably high mortality rates.

Troponin--a new marker in the diagnostics of muscle diseases in animals.

The dysfunction of muscles, especially that of the cardiac muscle, is one of the most dangerous for the life pathological states. The determination of biochemical indexes such as AST, ALT, CK, LDH, mioglobin, etc., which has been used so far in animals is not a sufficient diagnostic method. Therefore, new markers, levels of which could reflect the state of a patient more precisely, have been sought. Troponin, a protein found in skeletal and cardiac muscles only, has been considered a reliable index of myocardial ischemia in animals, especially in dogs. Its diagnostic properties have appeared to be a valuable complementation of the other diagnostic methods and thus could have gained a lot of veterinary practitioners interest.

The effect of agmatine administration on ischemic-reperfused isolated rat heart.

BACKGROUND: The natural polyamine Agmatine (Ag) plays a significant role in protection of nerve cell ischemic injury. A previous report indicated that Ag given intraperitoneally to rats enhanced the recovery of the heart from ischemic injury. Based on this initial observation, a larger investigation was undertaken to explore a dose-response effect and possible mechanisms underlying the protective effects. METHODS: Using the modified Langendorff model, 36 isolated hearts were divided into five groups: group 1, hearts receiving 100 microM/L Ag pre-ischemia (n=7); group 2, hearts receiving 100 microM/L Ag pre- and post-ischemia, (n=7); group 3, hearts receiving 250 microM/L Ag pre-ischemia (n=7); group 4, hearts receiving 250 microM/L Ag pre- and postischemia (n=7); and group 5, hearts receiving Krebs-Hensleit solution served as control (n=8). The study design included 20 minutes of perfusion, 30 minutes of global ischemia, and 30 minutes of reperfusion. RESULTS: After ischemia, group 2 developed higher left ventricular pressure P(max) (P<0.01), improved first-derivative of the rise (dP/dt max; P<0.02), and fall (dP/dt min; P<0.04) in left ventricular pressure, and the area calculated under the left-ventricle developed pressure curve (pressure-time integral; P<0.015), but coronary flow was not significantly increased (P=0.06) compared to the control group. Group 1 had improved diastolic recovery: dP/dt min (P<0.05) and coronary flow (P<0.03), compared with the control group. Group 3 had improved P(max) (P<0.01), dP/dt min (P<0.01), and coronary flow (P<0.02); group 4 had no improvement in all hemodynamic parameters. CONCLUSION: Low doses of Ag given pre- and post-ischemia, and high doses given only pre-ischemia have favorable, protective effects on the hemodynamic recovery of isolated rat heart undergoing global ischemia and reperfusion.