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Background: Non-steroidal anti-inflammatory drugs are considered today a very important group of medication, with a wide variety of therapeutic use, in different areas of modern medicine. Despite their beneficial effects on the patient, these drugs show a high incidence of side effects, mainly in the gastrointestinal tract. The physiopathological mechanisms of non-steroidal anti-inflammatory drugs induced lesions and the gastric mucosa defense mechanism became an important source for medical research, especially those which try to evaluate the role of nitric oxide as a cytoprotective agent., Aim: To define a possible cytoprotective effect of a nitric oxide donor, isosorbide dinitrate, on the gastric mucous of rats submitted to non-steroidal anti-inflammatory drugs ketoprofen treatment., Methods: Adult male Wistar rats, previously submitted to starvation for 24 hours and divided in three groups: group I (standard): animals that received isotonic saline solution intragastric by gavage and intravenous. Group II (control-ketoprofen): animals that received isotonic saline solution intragastric by gavage and ketoprofen intravenous. Group III (nitrate/ketoprofen): animals that received 2mM solution of isosorbide dinitrate intragastric by gavage and ketoprofen intravenous. Later on, these animals were sacrificed and had their stomach removed and submitted to macroscopical, microscopical and biochemical studies. The evaluated parameters were: a) gastric lesion index; b) gastric mucous layer thickness; c) gastric tissue nitrate/nitrite (NOx) concentration and d) gastric tissue malondialdehyde concentration., Results: a) Gastric lesion index evaluation showed a smaller statistically significant incidence on the animals of group III; b) group III showed a thicker mucous layer, which also was statistically significant, when compared to group II; c) the variation on tissue nitrate/nitrite concentration was similar in all three groups, without statistical significance when compared to each other., Conclusion: Isosorbide dinitrate has a cytoprotective activity on the gastric mucosa of rats submitted to ketoprofen action.

Sildenafil attenuates acute pulmonary embolism-induced pulmonary hypertension. However, the hemodynamic effects of sildenafil in combination with other vasodilators during acute pulmonary embolism have not been examined yet. In the present study, we examined the hemodynamic effects of combined sildenafil (0.25 mg/kg, i.v.) and L-arginine (100, 200, 500, and 1000 mg/kg/h, i.v.) in an anesthetized dog model of acute pulmonary embolism. Plasma nitrite/nitrate (NO(x)) and cGMP concentrations were determined using an ozone-based chemiluminescence assay and a commercial enzyme immunoassay, respectively. We found that L-arginine alone did not attenuate acute pulmonary embolism-induced pulmonary hypertension. However, significant decreases in mean pulmonary artery pressure were observed 30, 45, 60, and 75 min after the administration of sildenafil alone or after the combined administration of sildenafil and L-arginine (all P < 0.05). No significant differences among groups were observed in the respiratory parameters. While L-arginine significantly increased NO(x) concentrations, cGMP concentrations increased only when sildenafil was administered (all P < 0.05). These results suggest that while sildenafil attenuates acute pulmonary embolism-induced pulmonary hypertension, L-arginine does not enhance the beneficial hemodynamic effects of sildenafil. In addition, these findings suggest that stimulation of NO synthesis with L-arginine during acute pulmonary embolism does not produce beneficial effects.

It has been proposed that the acetylcholine (ACh)-induced relaxation of the rat aorta is entirely mediated by endothelium derived-nitric oxide (NO). However, some authors have reported that indomethacin pretreatment attenuates ACh-induced relaxation of rat aortic ring preparations. Moreover, it has also been suggested that cAMP accumulation may regulate either nitric oxide synthase (NOS) or cyclooxygenase (COX) expression in different tissues. Thus, in this in vitro study we have investigated the endothelial mechanisms involved in the ACh-induced relaxation of ring preparations of the rat thoracic aorta, as well as the influence chronic treatment with the selective beta(2)-agonist salbutamol had upon such mechanisms. Results of functional experiments show that N(G)-monomethyl-L-arginine (L-NMMA, 3 x 10(-4) M) considerably inhibited the ACh-induced relaxation of rat aortic ring preparations. However, indomethacin (10(-5) M) was also found to partially attenuate this ACh response, suggesting that although NO is the most important mediator of the ACh-induced relaxation of the rat aortic ring preparations, vasorelaxation may also involve prostanoids. Moreover, the results suggest that treatment with salbutamol failed to produce any change in the ACh-induced relaxation of rat aortic ring preparations.

In this study, the isolated use of methylene blue (MB) in the treatment of anaphylactic shock induced by Compound 48/80 (C48/80), a potent histamine releaser, was examined, and the study of the effects of MB on the function of the aorta artery endothelium was accomplished in vitro. MB was used in a single 3.0 mg/kg dose, and C48/80 was used in a single 4.5 mg/kg dose. The study protocol included the following experimental groups, containing six animals each: group I (control), animals in the absence of any drug action; group II (MB), MB infusion; Group III (C48/80), anaphylactic shock induced by using C48/80; group IV (C48/80 + MB), anaphylactic shock treated with MB infusion at the moment of major hypotension; and group V (MB + C48/80), prevention of anaphylactic shock with MB by means of MB infusion minutes before the 4.5 mg/kg C48/80 infusion. Nitric oxide plasma levels were measured in each of the experimental groups. After the in vivo studies were performed, an in vitro study was conducted using segments of the abdominal aortas of the rabbits to determine the effect of MB on the arterial endothelium. The results obtained in the present investigation have shown that MB intravenous infusion does not change the mean arterial pressure when compared with the control group (n = 6 in each group, P < 0.05); that C48/80 is effective in producing experimental anaphylactic shock (n = 6, P < 0.05); that the attempt to prevent anaphylactic shock with MB results in a mean prolongation of animal survival ranging from 17 to 34 min (n = 6 in each group, P < 0.05); that MB is effective in reversing anaphylactic shock in all the studied rabbits (n = 6, P < 0.05); that absolute and percentage plasma nitrate values obtained with the experimental groups do not differ (n = 6, each group, P < 0.05); and that the in vitro study of segments of abdominal aorta has shown that there has not been endothelial dysfunction in any of the groups (n = 6 in each group, P < 0.05). The good results obtained in this study open a research path that may offer data to define new paradigms for treating anaphylaxis.

To present our experience with penetrating cardiac injuries. We have retrospectively reviewed the records of 70 victims of penetrating cardiac injuries. A logistic regression has been performed in order to determine the association between death and clinical predictors. Penetrating injuries consisted of 43 stab wounds (61.4%) and 27 (38.6%) gunshot injuries (P=0.72). There were 63 (90%) male and 7 female (10%, P<0.001) victims. The mean age was 27.36+/-11.51, ranging from 3 to 65 years. The overall mortality was 32.9%, 47.8% for gunshot wounds and 52.2% for stab wounds (P=0.266). Eight victims (11.4%) had associated intra-thoracic great vessel injuries and 17 (24.3%) presented associated intra-abdominal organ injuries. The incidence of injured chamber was: right ventricle 37.1%, right atrium 27.1%, left ventricle 25.7%, and left atrium 5.7%. Non-survivors had lower systolic blood pressure (37.50+/-39.18 mmHg) than survivors (79.04+/-41.04 mmHg; P<0.001) upon arrival at the hospital. Thirteen non-survival (56.5%) and 10 (21.3%) survival victims had systolic blood pressure (SBP)

Background: Mitochondrial respiratory activity is associated with hepatic ischemia/reperfusion injury., Aim: To determine in vitro whether hepatic ischemia/reperfusion injury may be detected regardless mitochondrial respiratory activity., Material and Methods: Twenty-four heartworm-free mongrel dogs of either sex were randomized in the following groups: control, sham-operated dogs; I60, dogs subjected to 60 min of liver ischemia; I30/R60, dogs subjected to 30 min of ischemia e 60 min of reperfusion of liver; I45/R120 animals subjected to 45 min of ischemia and 120 min of reperfusion of liver. Blood and liver samples were taken after surgery to be processed. Mitochondrial respiratory activity was measured with a Clark-type oxygen electrode and mitochondrial membrane potential was calculated. lactic dehydrogenase, aspartate amino transferase and alanine aminotrasferase activities were determinated using laboratory kits, and malondialdehyde content in liver samples was estimated., Results: The group I45/R120 showed increases of serum aminotransferase, lactic dehydrogenase and malondialdehyde in liver samples. Whereas no changes were registered in mitochondrial respiratory activities and mitochondrial membrane potential, a tendency of decrease in the rate of active respiration (state 3) could be observed., Conclusion: Under the conditions of this study, the results suggest the data from mitochondrial respiratory activity could show no significance difference among groups in hepatic ischemia/reperfusion injury. Hepatic ischemia reperfusion injury can be detected regardless mitochondrial respiratory activity.

Objective: To assess the vasodilating effects of amiodarone on canine coronary arteries by using solutions of amiodarone dissolved in polysorbate 80 or water., Methods: Rings of coronary arteries, with or without intact endothelium, were immersed in Krebs solution and connected to a transducer for measuring the isometric force promoted by a vascular contraction. The arteries were exposed to increasing concentrations of polysorbate 80, amiodarone dissolved in water, amiodarone dissolved in polysorbate 80, and a commercial presentation of amiodarone (Cordarone). The experiments were conducted in the presence of the following enzymatic blockers: only indomethacin, Nomega-nitro-L-arginine associated with indomethacin, and only Nomega-nitro-L-arginine., Results: Polysorbate 80 caused a small degree of nonendothelium-dependent relaxation. Cordarone, amiodarone dissolved in water, and amiodarone dissolved in polysorbate 80 caused endothelium-dependent relaxation, which was greater for amiodarone dissolved in polysorbate and for Cordarone. Only the association of indomethacin and Nomega-nitro-L-arginine could eliminate the endothelium-dependent relaxation caused by amiodarone dissolved in polysorbate 80., Conclusion: The results obtained indicate that vasodilation promoted by amiodarone in canine coronary arteries is mainly caused by stimulation of the release of nitric oxide and cyclooxygenase-dependent relaxing endothelial factors.

The Wolff-Parkinson-White syndrome (WPW) and sinus venosus atrial septal defect (ASD) association is very rare and not yet reported in the literature. It is the main basis for this case report.

Selective pulmonary vasodilators attenuate acute pulmonary embolism (APE)-induced pulmonary hypertension. We examined the effects of intravenous sildenafil on the hemodynamic and respiratory changes caused by APE in anesthetized dogs. Sham operated animals (n=3) received only saline infusions. APE was induced by intravenous injections of microspheres in amounts adjusted to increase mean pulmonary artery pressures (MPAP) by 20 mmHg. Hemodynamic evaluation was performed and arterial blood samples were drawn for blood gas analysis at baseline, 15 and 30 min after APE was induced, and then 15, 30, and 45 min after the sildenafil infusion (1 mg kg(-1) infused intravenously in 15 min followed by 0.3 mg kg(-1) h(-1) for 30 min) started in the Sildenafil group (n=7), or saline infusion started in the control group (n=8). APE induced sustained pulmonary hypertension and 325% increase in pulmonary vascular resistance index (PVRI) without significant changes in the other hemodynamic parameters. While the animals in the control group showed no further changes in MPAP and PVRI, a significant decrease in MPAP and PVRI (-25 and -45%, respectively; P<0.05 both) was observed with sildenafil. No significant changes in the other hemodynamic parameters were observed in both groups. APE decreased PaO2, whereas sildenafil attenuated the decrease in PaO2 (P<0.05). We conclude that intravenous sildenafil can selectively attenuate the increases in MPAP and PVRI after APE.

This experimental investigation was carried out to study the endothelium-dependent ischemia-reperfusion injury upon the release of nitric oxide (NO) in the canine femoral artery. The tested experimental model was the inferior canine hindlimb ischemia induced by infrarenal abdominal aortic clamping followed by reperfusion. The research protocol was standardized in four experimental groups (n=6): (1) Control group; (2) Ischemia (120 minutes) group; (3) Ischemia (90 minutes) and reperfusion (60 minutes) group; and (4) Ischemia (120 minutes) and reperfusion (90 minutes) group. The femoral artery vascular reactivity was studied in vitro with the aid of an eight "organ chambers'' setup, where segments from 4 to 5 mm, with and without endothelium, were suspended and connected to force transducers. The fundamental data of this study were as follows: (1) Ischemia caused by 120 minutes of infrarenal aortic clamping did not cause femoral artery endothelium dysfunction. (2) Ischemia caused by 90 minutes of clamping followed by 60 minutes of reperfusion also did not cause endothelium dysfunction, with an observed tendency to signal transduction impairment (studied by the sodium fluoride dose response curves). (3) Ischemia caused by 120 minutes of clamping followed by 90 minutes of reperfusion caused endothelium dysfunction, observed by the femoral artery impaired capacity of the endothelium-dependent NO release evoked by acetylcholine, adenosine diphosphate, and sodium fluoride. The present pharmacologic in vitro observations are concordant with the evidence that the NO-release impairment, caused by inferior canine hindlimb ischemia followed by reperfusion, is a consequence of endothelium cell membrane receptors, and G-proteins signal transduction dysfunction.

Background and Objectives: The risk of perioperative anaphylaxis should always be considered. The incidence of anesthetic allergic reactions is controversial, varying from 1/3,000 to 1/20,000, with mortality range between 3 and 9%. This report describes the use of methylene blue as coadjuvant drug to treat anaphylaxis refractory to conventional therapy., Case Report: A 53-year-old male patient was submitted to inguinal hernia correction under spinal anesthesia. After receiving 1.5 g intravenous dipirone at surgery completion, he immediately developed bronchospasm, cyanosis, decreased SpO2 and SBP, culminating with cardiac arrest. Resuscitation was started with external cardiac massage followed by tracheal intubation, as well as 1 mg epinephrine and 1 mg atropine injections. Heart rate returned (150 bpm) with no palpable pulse though. Additional 1 mg epinephrine and 1 g hydrocortisone were administered with central pulse recovery (8 minutes). Although receiving dopamine (20 microg.kg-1.min-1), patient remained hypotensive (60 mmHg) until 80 minutes. Intravenous 100 mg methylene blue was then administered with increased SBP to 85 and 105 mmHg after the second dose. Dopamine dose was tapered from 10 to 7, 5 and finally 2 microg.kg-1.min-1., Conclusions: Histamine is the major anaphylaxis mediator. Inducing nitric oxide (NO) production, it consequently increases guanylate cyclase, which promotes arteriolar vasodilation by increasing cyclic GMP. Methylene blue may be helpful in such situations because it inhibits guanylate cyclase and consequently vasodilation, resulting in hemodynamic improvement.

The present study investigated the protective effect of N-acetylcysteine (NAC) against oxygen radical-mediated coronary artery injury. Vascular contraction and relaxation were determined in canine coronary arteries immersed in Kreb's solution (95% O2-5% CO2), incubated or not with NAC (10 mM), and exposed to free radicals (FR) generated by xanthine oxidase (100 mU/ml) plus xanthine (0.1 mM). Rings not exposed to FR or NAC were used as controls. The arteries were contracted with 2.5 microM prostaglandin F2alpha. Subsequently, concentration-response curves for acetylcholine, calcium ionophore and sodium fluoride were obtained in the presence of 20 microM indomethacin. Concentration-response curves for bradykinin, calcium ionophore, sodium nitroprusside, and pinacidil were obtained in the presence of indomethacin plus Nomega-nitro-L-arginine (0.2 mM). The oxidative stress reduced the vascular contraction of arteries not exposed to NAC (3.93 +/- 3.42 g), compared to control (8.56 +/- 3.16 g) and to NAC group (9.07 +/- 4.0 g). Additionally, in arteries not exposed to NAC the endothelium-dependent nitric oxide (NO)-dependent relaxation promoted by acetylcholine (1 nM to 10 microM) was also reduced (maximal relaxation of 52.1 +/- 43.2%), compared to control (100%) and NAC group (97.0 +/- 4.3%), as well as the NO/cyclooxygenase-independent receptor-dependent relaxation provoked by bradykinin (1 nM to 10 microM; maximal relaxation of 20.0 +/- 21.2%), compared to control (100%) and NAC group (70.8 +/- 20.0%). The endothelium-independent relaxation elicited by sodium nitroprusside (1 nM to 1 microM) and pinacidil (1 nM to 10 microM) was not affected. In conclusion, the vascular dysfunction caused by the oxidative stress, expressed as reduction of the endothelium-dependent relaxation and of the vascular smooth muscle contraction, was prevented by NAC.

We present a new surgical technique for patent ductus arteriosus (PDA) occlusion in premature neonates (PN). Through a dorsal minithoracotomy the PDA is dissected extrapleurally with q-tips and clipped. The short surgical time, avoidance of pleural drainage, and prevention of late breast deformity are the operation highlights.

To determine if radiocontrast impairs vascular relaxation of the renal artery, segments (4-5 mm in length) of canine renal artery were suspended in vitro in organ chambers to measure isometric force (95% O2/5% CO2, at 37 C). Arterial segments with and without endothelium were placed at the optimal point of their length-tension relation and incubated with 10 microM indomethacin to prevent synthesis of endogenous prostanoids. The presence of nonionic radiocontrast (iohexol, Omnipaque 350, 1 ml in 25 ml control solution, 4% (v/v)) did not alter endothelium-dependent relaxation to acetylcholine in rings precontracted with both norepinephrine and prostaglandin F2alpha (N = 6). When the rings were precontracted with prostaglandin F2alpha, the presence of ionic contrast did not inhibit the relaxation of the arteries. However, in canine renal arteries contracted with norepinephrine, the presence of ionic radiocontrast (diatrizoate meglumine and diatrizoate sodium, MD-76, 1 ml in 25 ml control solution, 4% (v/v)) inhibited relaxation in response to acetylcholine, sodium nitroprusside (N = 6 in each group), and isoproterenol (N = 5; P < 0.05). Rings were relaxed less than 50% of norepinephrine contraction. Following removal of the contrast, vascular relaxation in response to the agonists returned to normal. These results indicate that ionic radiocontrast nonspecifically inhibits vasodilation (both cAMP-mediated and cGMP-mediated) of canine renal arteries contracted with norepinephrine. This reversible impairment of vasodilation could inhibit normal renal perfusion and act as a mechanism of renal failure following radiocontrast infusion. In the adopted experimental protocol the isoproterenol-induced relaxation of renal arteries precontracted with norepinephrine was more affected, suggesting a pivotal role of the cAMP system.

Background: The purpose of this paper is to propose methylene blue as a lifesaving alternative drug for the treatment of contrast-induced anaphylaxis., Case Report: In a cardiovascular catheterization laboratory invasive hemodynamic monitoring was used to document the lifesaving effect of IV bolus injections of 1.5-2 mg/Kg methylene blue solution to treat three patients for anaphylactic shock following radiocontrast injection during coronary angiography. Methylene blue administration was followed by prompt circulatory improvement, leading to hemodynamic stabilization and relief of other anaphylactic symptoms in each case. There were no deaths., Conclusions: Our findings suggest that methylene blue can be lifesaving in anaphylactic shock, notwithstanding some transitory side effects, such as cardiac rhythm disturbances and chest pain, both of which possibly originate from sudden myocardial perfusion deficits.

Objective: To study the role of magnesium in the endothelial dysfunction of canine coronary arteries caused by cardiopulmonary bypass (CPB) global ischemia followed by reperfusion., Design: Segments of canine coronary arteries were suspended in organ chambers to measure isometric contraction by prostaglandin F (2alpha), and relaxed by acetylcholine (ACh), sodium fluoride (NaF), calcium ionophore (A23187) and sodium nitroprusside (SNP) in crescent concentrations. The investigation protocol had groups with six dogs: CONTROL group (without CPB), CPB group (105 min of CPB without aortic cross-clamping), ISCH group (45 min of CPB with aortic cross-clamping), ISCH/REP group (45 min of aortic cross-clamping followed by 60 min of reperfusion). The coronary relaxations were evaluated with (phase I), without (phase II) and restored magnesium (phase III) to the organ bath., Results: The presence of magnesium in the organ bath was associated with the greater relaxation in response to agonists of the nitric oxide production. The removal of magnesium from the organ bath was associated with the reduction in the intensity of vessel relaxation. The magnesium restoration to the organ bath was associated with the additional reduction in the intensity of relaxation with the exception of NaF that allowed re-acquisition of the relaxation observed in the presence of magnesium., Conclusion: This in vitro study demonstrates that magnesium ion favorably influences the nitric oxide production by the coronary endothelium, attenuating the endothelial dysfunction caused by global ischemia followed by reperfusion.

A case of left atrial myxoma is reported in a 14-year-old female patient with recurrent episodes of syncope. The patient was immediately referred to the cardiologist after an inconclusive neurological investigation. Syncope is a symptom thoroughly described as being associated with heart myxomas, but its specific association with adolescence is extremely rare. The authors discuss the clinical manifestations of the disease, emphasizing the diagnostic difficulties on the basis of the unspecific symptoms. As part of the analysis a Brazilian literature review was carried out. Also, the authors experience in the surgical treatment of the heart tumors is briefly presented.

Objective: To study the mechanism by which poly-L-arginine mediates endothelium-dependent relaxation., Methods: Vascular segments with and without endothelium were suspended in organ chambers filled with control solution maintained at 37 C and bubbled with 95% O2 / 5% CO2. Used drugs: indomethacin, acetycholine, EGTA, glybenclamide, ouabain, poly-L-arginine, methylene blue, N G-nitro-L-arginine, and verapamil and N G-monomethyl-L-arginine. Prostaglandin F2 and potassium chloride were used to contract the vascular rings., Results: Poly-L-arginine (10-11 to 10-7 M) induced concentration-dependent relaxation in coronary artery segments with endothelium. The relaxation to poly-L-arginine was attenuated by ouabain, but was unaffected by glybenclamide. L-NOARG and oxyhemoglobin caused attenuation, but did not abolish this relaxation. Also, the relaxations was unaffected by methylene blue, verapamil, or the presence of a calcium-free bathing medium. The endothelium-dependent to poly-L-arginine relaxation was abolished only in vessels contracted with potassium chloride (40 mM) in the presence of L-NOARG and indomethacin., Conclusion: These experiments indicate that poly-L-arginine induces relaxation independent of nitric oxide.

Objective: To determine whether arginine vasopressin releases endothelium-derived nitric oxide (EDNO) from the epicardial coronary artery., Methods: We studied segments of canine left circumflex coronary arteries suspended in organ chambers to measure isometric force. The coronary artery segments were contracted with prostaglandin F2alpha (2 x 10-6M) and exposed to a unique, strong arginine vasopressin concentration (10-6M) or titrated concentrations (10-9 a 10-5 M)., Results: The unique dose of arginine vasopressin concentration (10-6M) induced transient, but significant (p<0.05), relaxation in arterial segments with endothelium, and an increase, not significant, in tension in arteries without endothelium. Endothelium-dependent relaxation to arginine vasopressin was inhibited by Ng-monomethyl-L-arginine (L-NMMA, 10-5M) or N G-nitro-L-arginine (L-NOARG) (10-4M), 2 inhibitors of nitric oxide synthesis from L-arginine. Exogenous L-arginine (10-4M), but not D-arginine (10-4M), reversed the inhibitory effect of L-NMMA on vasopressin-mediated vasorelaxation. Endothelium dependent relaxation to vasopressin was also reversibly inhibited by the vasopressin V1-receptor blocker d(CH2)5Try(Me) arginine vasopressin (10-6M) (n=6, P<0.05)., Conclusion: Vasopressin acts through V1 endothelial receptors to stimulate nitric oxide release from L-arginine.

The endothelium-dependent relaxation elicited by poly-L-arginine was investigated in canine coronary arteries. Poly-L-arginine (10(-11) to 10(-7) M) induced concentration-dependent endothelium-dependent relaxation in segments of canine coronary arteries incubated with indomethacin. In the presence of indomethacin, arteries contracted with prostaglandin F2alpha and exposed also to ouabain, oxyhemoglobin, or N(omega)-nitro-L-arginine, as well as those contracted with 20 mM of KCl, presented reduced endothelium-dependent relaxation to poly-L-arginine. The combination of N(omega)-nitro-L-arginine with indomethacin produced further reduction of endothelium-dependent relaxation in arteries contracted with prostaglandin F2alpha as well as in arteries contracted with 20 mM of KCl. However, only quinacrine or calmidazolium, both in presence of N(omega)-nitro-L-arginine plus indomethacin, abolished the endothelium-dependent relaxation elicited by poly-L-arginine. The relaxation to poly-L-arginine was not significantly affected by glybenclamide. The present study demonstrates that in addition to the prostacyclin and nitric oxide-dependent mechanisms, poly-L-arginine also elicits endothelium-dependent relaxation in canine coronary arteries, stimulating the release of endothelial relaxing factor(s) produced by the phospholipase A2 pathway, but independent of the cyclooxygenase pathway, which may cause hyperpolarization of the vascular smooth muscle.

Background: The purpose of this experiment was four-fold: 1) to determine the effect of currently used cardiovascular drugs on internal mammary artery (IMA) vascular tone, 2) to examine IMA reactivity to autacoids and products released from aggregating platelets, 3) to compare the vascular reactivity of the right versus left IMA, and 4) to determine whether the canine IMA was an acceptable physiological model as regards its similarity to the human IMA, which is used routinely for coronary artery bypass grafting., Methods: To study factors that modulate the tone of IMA, bypass grafts, right and left canine IMAs were studied in vitro in organ chambers (95% O(2)/5% CO(2), pH=7.4)., Results: Increasing concentrations (10(-9) to 10(-4M)) of the neurotransmitter acetylcholine (ACH) and the platelet-derived products adenosine diphosphate (ADP) or serotonin (5-HT) induced vasodilatation of contracted right and left IMAs. The vasodilation caused by ACH and ADP was endothelium-dependent while serotonin acted directly on the vascular smooth muscle. Histamine and bradykinin also induced IMA vasodilation, histamine via a direct action on the smooth muscle, and bradykinin through the release of nitric oxide (NO). In canine IMAs, the calcium ionophore A23187 produced endothelium-dependent vasodilation of contracted blood vessels; this vasodilation was blocked by N(G)-nitro-L-arginine (10(-4)M), a competitive inhibitor of nitric oxide synthesis from L-arginine, and by hemoglobin (10(-5)M). Dopamine, dobutamine, and papaverine induced vasodilation of the IMA regardless of the presence or absence of an intact intima, while norepinephrine induced profound IMA vasoconstriction, which was comparable to contraction to potassium ions or the constrictor peptide endothelin., Conclusions: These experiments establish a pharmacological profile of IMA and demonstrate that endogenous and exogenous compounds can significantly alter its vascular tone.

Clinical and experimental observations prove that heparin-neutralizing doses of protamine increase pulmonary artery pressures and decrease systemic BP. Protamine also increases myocardial oxygen consumption, cardiac output, and heart rate, and decreases systemic vascular resistance. These cardiovascular effects have clinical consequences that have justified studies in this area. Protamine adverse reactions usually have three different categories: systemic hypotension, anaphylactoid reactions, and catastrophic pulmonary vasoconstriction. The precise mechanism that explains protamine-mediated systemic hypotension is unknown. Four experimental protocols performed at Mayo Clinic, Rochester, MN, studied the intrinsic mechanism of protamine vasodilation. The first study reported in vitro systemic and coronary vasodilation after protamine infusion. The second in vitro study suggested that the pulmonary circulation is extensively involved in the protamine-mediated effects on endothelial function. The third study, carried out in anesthetized dogs, reported the methylene blue and nitric oxide synthase blockers neutralization of the protamine vasodilatatory effects. The fourth study suggested that protamine also causes endothelium-dependent vasodilation in heart microvessels and conductance arteries by different mechanisms including hyperpolarization. Reviewing these experimental results and our clinical experience, we suggest methylene blue as a novel approach to prevent and treat hemodynamic complications caused by the use of protamine after cardiopulmonary bypass. In the absence of prospective clinical trials, a growing body of cumulative clinical evidence suggests that methylene blue may be strongly considered as a therapeutic approach in the treatment of distributive shock.

Submitral left ventricular aneurysm is a cardiac pathology widely recognized, but relatively unknown, occurred almost exclusively in African black patients. Although still this idea of racial prevalence exists, cases have been described in patients of all the races. Ten Brazilian cases were reported. One of them was presented inside an Italian paper that refers the surgical treatment of a Brazilian patient of black race. We reported one more submitral left ventricular aneurysm case in a brown female patient, with antecedents of peripheral thromboembolism initially not identified as consequence of the cardiac pathology.

Objective: Hyaluronidase, an endogenous enzyme that hydrolyzes mucopolysaccharides, has been shown to enhance myocardial protection when added to preservation solutions. In addition, hyaluronidase infusion reduces injury to ischemic myocardium. Endothelium-derived nitric oxide is an endogenous vasodilator that prevents leukocyte adhesion to the intima and inhibits platelet adhesion and aggregation in the coronary artery. Experiments were undertaken to determine whether the protective action of hyaluronidase could be mediated by the endogenous release of nitric oxide., Methods: Segments of coronary artery, with and without endothelium, were placed in organ chambers (25 mL) to measure isometric force. Blood vessel segments were contracted with prostaglandin F(2)(alpha) (2 x 10(-6) mol/L) and exposed to hyaluronidase (3-15 units)., Results: Hyaluronidase induced vasodilation of arteries with intact endothelium but not of arteries without endothelium (n = 6, P<.05). Endothelium-dependent vasodilation to hyaluronidase was blocked by N(G)-monomethyl-L -arginine (10(-5) mol/L), an inhibitor of nitric oxide synthesis from L -arginine (n = 6, P<.05). Inhibition of vasodilation by N(G)-monomethyl-L -arginine was reversed by L -arginine (10(-4) mol/L) but not D -arginine (10(-4) mol/L; n = 6, each group). Vasodilation to hyaluronidase also was inhibited by hemoglobin (2 x 10(-6) mol/L), a scavenger of the nitric oxide radical (n = 6, P<.05)., Conclusions: Hyaluronidase induces the release of nitric oxide from the coronary endothelium. Because nitric oxide, an endogenous vasodilator, inhibits leukocyte adhesion to the intima in addition to inhibiting platelet adhesion and aggregation, stimulated production of endothelium-derived nitric oxide by exogenous hyaluronidase could be the mechanism of the protective action of hyaluronidase infusion.

A patient with heart failure and acute atrial fibrillation received the final diagnosis of atrial infarction associated with ventricular infarction based on clinical findings of ischemia in association with atrial fibrillation and heart failure (mechanisms probably involved: contractile dysfunction and loss of atrial contribution). Although a transesophageal echocardiography, which could refine the diagnosis of anatomic abnormalities, was not performed, all evidence led to the diagnosis of atrial involvement. Electrocardiographic findings were consistent with Liu's major criterion 3. Therapy with digitalis, quinidine and angiotensin-converting enzyme inhibitors was chosen, as the patient had acute pulmonary edema. The use of beta-blockers and verapamil was res-tricted. No other complications, such as thrombo-embolism or atrial rupture, were noted.

Early systemic arterial hypotension is a common clinical feature of Pseudomonas septicemia. To determine if Pseudomonas aeruginosa endotoxin induces the release of endothelium-derived nitric oxide (EDNO), an endogenous nitrovasodilator, segments of canine femoral, renal, hepatic, superior mesenteric, and left circumflex coronary arteries were suspended in organ chambers (physiological salt solution, 95% O2/5% CO2, pH 7.4, 37 degrees C) to measure isometric force. In arterial segments contracted with 2 microM prostaglandin F2 alpha, Pseudomonas endotoxin (lipopolysaccharide (LPS) serotype 10(Habs) from Pseudomonas aeruginosa (0.05 to 0.50 mg/ml) induced concentration-dependent relaxation of segments with endothelium (P < 0.05) but no significant change in tension of arteries without endothelium. Endothelium-dependent relaxation in response to Pseudomonas LPS occurred in the presence of 1 microM indomethacin, but could be blocked in the coronary artery with 10 microM NG-monomethyl-L-arginine (L-NMMA), a competitive inhibitor of nitric oxide synthesis from L-arginine. The inhibitory effect of L-NMMA on LPS-mediated vasorelaxation of the coronary artery could be reversed by exogenous 100 microM L-arginine but not by 100 microM D-arginine. These experiments indicate that Pseudomonas endotoxin induces synthesis of nitric oxide from L-arginine by the vascular endothelium. LPS-mediated production of EDNO by the endothelium, possibly through the action of constitutive nitric oxide synthase (NOSc), may decrease systemic vascular resistance and may be the mechanism of early hypotension characteristic of Pseudomonas septicemia.

Background: Greater release of endothelium-derived nitric oxide is implicated in the superior patency of the internal mammary artery (IMA) used in coronary artery bypass grafting. This study compared the release of endothelium-derived nitric oxide into the lumen of the IMA and the saphenous vein under normoxic versus hypoxic conditions., Methods: Segments of canine IMA and saphenous vein were perfused in vitro. Vasorelaxant activity was measured as vasodilatation of coronary artery smooth muscle induced by the effluent., Results: Effluents from the IMA and saphenous vein caused comparable vasodilation of coronary artery smooth muscle. The vasodilatation reversed when perfusion was switched to a prosthetic conduit. Vasodilator activity from the IMA and saphenous vein was attenuated by removing the intima of the grafts or by adding N(G)-monomethyl-L-arginine (10(-4) mol/L) or N(G)-nitro-L-arginine (10(-4) mol/L), two inhibitors of nitric oxide synthesis. Indomethacin attenuated vasorelaxant activity from saphenous vein grafts but not IMA grafts (n = 10). Vasodilator release from the IMA and saphenous vein was augmented by hypoxia. This augmentation was inhibited by indomethacin (n = 10, p < 0.05). Hypoxic augmentation reversed with return to normoxia., Conclusions: The release of endothelium-derived nitric oxide and prostacyclin from bypass grafts into the lumen, particularly during hypoxemia, could promote the vasodilation of distal coronary arterial beds, enhancing myocardial perfusion.

Background: Postoperative hypomagnesemia is common in patients who have undergone cardiac operations and is associated with clinically significant morbidity resulting from atrial and ventricular dysrhythmias. Magnesium supplementation may increase the cardiac index in the early postoperative period., Methods: The action of the magnesium cation on coronary vascular reactivity was studied. Segments of canine epicardial coronary artery were suspended in organ chambers to measure isometric force (95% O2/5% CO2, 37 degrees C)., Results: In coronary segments constricted with prostaglandin F2alpha (2 x 10[-6] mol/L), acetylcholine and adenosine diphosphate (10[-9] to 10[-4] mol/L) induced vasodilation in arteries with endothelium (n=10, each group; p < 0.05). Acetylcholine-mediated vasodilation was blocked by NG-monomethyl-L-arginine (10[-4] mol/L) and NG-nitro-L-arginine (10[-4] mol/L), two inhibitors of nitric oxide synthesis from L-arginine (n=10, p < 0.05). The removal of magnesium from the organ chamber solution impaired vasodilation in response to acetylcholine and adenosine diphosphate. However, normal endothelium-dependent vasodilation could be restored by return of magnesium to the bathing solution. Vascular relaxation in response to bradykinin (10[-9] to 10[-6] mol/L), which was found to induce endothelium-dependent vasodilation independent of nitric oxide production, was unaffected by magnesium removal (n=10)., Conclusions: Hypomagnesemia selectively impaired the release of nitric oxide from the coronary endothelium. Because nitric oxide is a potent endogenous nitro-vasodilator and inhibitor of platelet aggregation and adhesion, hypomagnesemia could promote vasoconstriction and coronary thrombosis in the early postoperative period.

This is the case of a 42 year-old male with systemic amyloidosis, probably primary, and heart involvement. Physiopathological and clinical aspects are described as well as the rarity of the diagnosis in vivo. The limited aspects of therapy are also described.

A case of newborn intrapericardial teratoma is reported. The clinical, echocardiographic, tomographic and histologic features are described, and also, the therapeutic options. The newborn was submitted to surgical excision of the intrapericardial tumor and has a clinical follow-up greater than four years.

We report a permanent complete heart block, in a 27 year-old female patient, developed during mitral percutaneous valvotomy using a single inflation of the Inoue balloon catheter. After one month, even using corticoids, a Mobitz II second-degree atrioventricular block persisted, the patient became symptomatic to moderate efforts and a cardiac pacemaker was implanted.

Background: Protamine sulfate, which is used for heparin neutralization, has been reported to induce catastrophic pulmonary vasoconstriction after infusion. However, in the systemic circulation, protamine infusion induces hypotension due to peripheral vasodilation., Methods: To determine whether protamine also could induce vasodilation in the pulmonary circulation, third-order canine pulmonary artery segments were studied in vitro in organ chambers., Results: In pulmonary artery segments that were caused to contract with phenylephrine (10(-5) mol/L), protamine sulfate (40 to 400 micrograms/mL, final organ bath concentration) produced concentration-dependent relaxation in canine pulmonary artery segments with endothelium (to 74% +/- 7% of the initial contraction to phenylephrine) that was significantly greater (p < 0.05) than in segments without endothelium (30% +/- 6% of the initial phenylephrine contraction). Pretreatment of arterial segments with NG-monomethyl-L-arginine (10(-5) mol/L), the competitive inhibitor of nitric oxide synthesis from L-arginine, did not change tension of arterial segments, but NG-monomethyl-L-arginine attenuated the relaxation to protamine. The inhibitory effect of NG-monomethyl-L-arginine could be reversed by the addition of L-arginine (10(-4) mol/L) but not D-arginine (10(-4) mol/L). Endothelium-dependent vasodilation to protamine (40 to 400 micrograms/mL) also could be inhibited by heparin (8 U/mL, final organ bath concentration). However, the inhibitory effect of heparin could be overcome by adding higher concentrations of protamine., Conclusions: Protamine-mediated pulmonary vasodilatation could be an important mechanism to protect against the constrictive effects of autocoids generated during heparin neutralization. Such a mechanism might be dysfunctional in certain persons and put them at risk for pulmonary vasoconstriction after protamine infusion.

Nitric oxide is a potent vasodilator and antiplatelet substance released by the vascular endothelium. In the current study, isolated rabbit hearts were perfused retrograde in the aortic root with a balanced salt solution using a Langendorff technique. To perfuse the right cardiac chambers, an inflow cannula was placed in the superior vena cava and an outflow cannula in the right ventricular apex via the pulmonary artery. To detect endocardial vasodilator production, right heart perfusate was used to bathe a "bioassay" segment of canine coronary artery denuded of endothelium. Perfusate from unstimulated hearts did not alter smooth muscle tone in the bioassay tissue. Calcium inophore, a potent stimulus for endothelial nitric oxide production, produced relaxation of the bioassay smooth muscle when added to the cardiac perfusate but not when applied directly to the bioassay segment. Cardiac effluent vasodilator activity was abolished by removal of the endocardium or addition of nitric oxide synthesis inhibitors, but not by prostanoid inhibitors. These experiments describe a practical method to bioassay endocardial nitric oxide production in the beating heart.

A 48-year-old man submitted to surgical excision of a left atrium leiomyosarcoma. The patient had a node close to the right suprarenal gland. The tumor was a casual echocardiographic finding as part of the cardiologic investigation, since the patient had shortness breath. Leiomyosarcomas of the heart are uncommon, and often the diagnosis is performed during postmortem examinations. Methods of diagnosis, specially the echocardiogram, were emphasised. Treatment and prognostic aspects on basis in a wide review of the literature were also emphasised.

This study was done to determine whether abnormal receptor-dependent release of endothelium-derived relaxing factor (EDRF) might be caused by G-protein dysfunction. Dogs were exposed to global myocardial ischemia (45 minutes, induced by aortic cross-clamping) followed by reperfusion (60 minutes) while on cardiopulmonary bypass, and coronary arteries were then studied in vitro in organ chamber experiments. After reperfusion, endothelium-dependent relaxation to the receptor-dependent agonists adenosine diphosphate and acetyl-choline was significantly impaired as well as to sodium fluoride, which acts on a pertussis toxin-sensitive G-protein. In contrast, endothelium-dependent relaxations to the receptor-independent agonists A23187 and phospholipase C were normal. Furthermore, endothelium-dependent relaxation to poly-L-arginine (molecular weight, 139,200), which appears to induce endothelium-dependent relaxation of the canine coronary artery by a nonnitric oxide pathway, was unaffected by ischemia and reperfusion. These experiments suggest that global myocardial ischemia and reperfusion selectively impair receptor-mediated release of EDRF (nitric oxide) but that the ability of the endothelial cell to produce EDRF or generate endothelium-dependent relaxation to nonnitric oxide-dependent agonists remains intact. We hypothesize that coronary reperfusion injury leads to G-protein dysfunction in the endothelium.

Background: Most prior physiological studies of the endothelium of intact saphenous veins have used organ chambers to assay abluminal release of vasoactive factors that affect smooth muscle contraction and relaxation. However, intraluminal release of vasoactive factors may have important implications in saphenous vein bypass graft patency., Methods and Results: To study the basal and stimulated intraluminal release of endothelium-dependent relaxing factor (EDRF), 5-cm segments of human saphenous veins were cannulated and perfused in vitro with physiological salt solution. Vasoactive properties of the effluent were bioassayed on canine coronary artery smooth muscle. Effluent from saphenous veins produced vasodilation of 4.0 +/- 1.8% (+/- SEM) (n = 26) under basal conditions and 36.1 +/- 6.7% when stimulated with calcium ionophore, A23187 (n = 19, P < .05). Fourteen of the 26 vein segments showed no basal release of EDRF. Vasodilation produced by the effluent could be eliminated by mechanically removing the endothelium or by treatment with NG-monomethyl-L-arginine or NG-nitro-L-arginine, two competitive inhibitors of nitric oxide synthesis from L-arginine. Vasodilation was not influenced by indomethacin., Conclusions: Previous studies of EDRF from human saphenous veins were performed in organ chambers, which could detect only extraluminal EDRF release. This is the first demonstration of intraluminal release of EDRF from human saphenous veins. The variable and relatively poor basal release of EDRF into the lumen may account for early thrombogenicity of vein grafts and may contribute to late atherosclerosis.