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Ricardo J Gelpi

Publications and source records attributed to Ricardo J Gelpi.

16 recordsLinked to original sources
PubMed2006

Ischemia and apoptosis in an animal model of permanent infarct-related artery occlusion.

Apoptosis is a pathologic feature of cardiomyocytes in acute myocardial infarction (AMI) and heart failure. The temporal course of apoptosis in the peri-infarct area in the weeks following an AMI is still uncompletely defined. In order to study the time course of apoptosis after AMI, 16 rabbits underwent left coronary artery ligation and were sacrificed at 16, 26, 35, and 56 days after surgery. Increased apoptotic rate (AR) was observed at in the peri-infarct region than in remote myocardium (5.4% [2.5-9.6] vs 0.4% [0.1-0.9], respectively, P<0.001) and than in sham-operated cases (0.01% [0-0.02], P<0.001). A gradual decrease of AR in the peri-infarct region was observed over time with a 90% reduction at 8 weeks after coronary ligation.

Animals↗
PubMed2006

Irinotecan-eluting stents inhibited neointimal proliferation in hypercholesterolemic rabbit aortas.

OBJECTIVE: To assess the effect of irinotecan-eluting stents (IS) on neointimal growth in the aortas of hypercholesterolemic rabbits and to determine other local histopathological effects such as necrosis, fibrin, and inflammatory reaction. METHODS: Phosphorylcholine-coated stents were deployed in the aortas of hypercholesterolemic rabbits. Group 1 (control; n = 8) received unloaded stents, group 2 (n = 7) and group 3 (n = 9) received IS with 0.046 mg and 1.29 mg of irinotecan, respectively. Eight weeks after implantation the rabbits were killed. Neointimal thickness (NT) was assessed by morphometry. Semiquantitative injury score (from 0 to 3+) was used to analyze inflammatory infiltrate, fibrin deposits, and necrosis in the stented segments. RESULTS: NT was reduced only in high-doses IS (G1, 167.4 +/- 20.8 mu; G2, 170.24 +/- 21.2 mu; G3, 111.56 +/- 12.7 mu; P < 0.05, G3 vs G1 and G2). Necrosis decreased significantly with IS [1.00 +/- 0.10 in G1 to 0.33 +/- 0.07 and 0.02 +/- 0.01 in G2 and G3, respectively] only in the media layer. The inflammatory infiltrate was present in the three layers of aortas from G1, but only decreased significantly in the intimae layer of the high-dose group [1.50 +/- 0.15 in G1 vs 1.00 +/- 0.18 in G3, P < 0.05]. CONCLUSION: Stents loaded with high-dose irinotecan inhibit NT in the aortas of hypercholesterolemic rabbits. This effect was accompanied by decreased inflammatory infiltrate and media necrosis.

Animals↗
PubMed2006

Effects of low-calcium reperfusion and adenosine on diastolic behavior during the transitory systolic overshoot of the stunned myocardium in the rabbit.

The aims of the present study were to determine whether the transitory systolic overshoot (TSO) that occurs in the early reperfusion (R) of the stunned myocardium is accompanied by diastolic alterations, and to determine whether the R with low Ca2+ Krebs-Henseleit's solution or with adenosine modifies these alterations. Isolated-isovolumic rabbit hearts were divided in 3 groups (G). G1 (n = 11) was perfused with Krebs-Henseleit's solution, subjected to 15 min of global ischemia and 30 min R; G2 (n = 10) was reperfused during the first 10 min with Krebs-Henseleit's solution [Ca2+] = 1 mmol/L, which was increased in the perfusate to 1.5 mmol/L up to 20 min R and at 2.5 mmol/L from 20 to 30 min R. G3 (n = 12) was perfused with Krebs-Henseleit's solution with adenosine (0.03 microg x kg(-1) x min(-1)) from 10 min before ischemia and during all R. Left ventricular (LV) +dP/dtmax (mmHg/s), LV end diastolic pressure (LVEDP, mmHg), and 1 relaxation index (t(1/2)) were measured in preischemic state, at 30, 50, 60, 70, 90, and 120 s R, and then at 5 and 30 min R. The +dP/dtmax recovered to 621 +/- 77 mmHg/s (p > 0.05), 346 +/- 31 mmHg/s (p < 0.05 vs. G1), and 533 +/- 76 mmHg/s (p > 0.05) from preischemic value of 730 +/- 39, 690 +/- 32, and 758 +/- 57 in G1, G2, and G3, respectively. The LVEDP in G1 and G3 increased early in the R, and it was negatively correlated with the +dP/dtmax (r = -0.63, p = 0.0369; and r = -0.71, p = 0.0090, respectively). The R with low Ca2+ abolished this correlation and attenuated the TSO phase. The correlation between LVEDP and +dP/dtmax in G1 and G3 and the lack of correlation in G2 suggests there are common mechanisms for the systolic and diastolic alterations during the TSO phase that are possibly related to Ca2+ overload but not with the vascular tone.

Adenosine↗
PubMed2006

[Evaluation of diastolic function during and post-exercise in patients with arterial hypertension].

UNLABELLED: It is known that patients with arterial hypertension and ventricular hypertrophy have diastolic alterations, in particular during exercise. However, it is controversial if diastolic dysfunction continues once exercise had concluded. The objective was to assess the effects of isometric exercise on the diastolic function in patients with arterial hypertension. Five control patients (group 1, G1) and 7 patients with arterial hypertension (group 2, G2) were studied. All patients underwent cardiac catheterization and performed isometric exercise until heart rate increased 43 +/- 7%. Left ventricular systolic pressure (LVSP) and end diastolic pressure (LVEDP) were measured. We calculated, +dP/dt(max), the time constant of isovolumic pressure decay (tau) and t1/2 were all measured. RESULTS: The LVSP increased in G1 and G2 during exercise from 140 +/- 3 to 195 +/- 14 mm Hg (p < 0.05) and 161 +/- 9 to 238 +/- 15 mm Hg, respectively; returning to their basal values once exercise had concluded. The tau (tau) and t1/2 increased, while exercising in G2, from 23 +/- 2 and 15 +/- 2 msec to 35 +/- 7 and 23 +/- 4 msec, respectively. After exercise both variables continued elevated reaching 41 +/- 6 msec (p < 0.05) and 23 +/- 3 msec (p < 0.05), respectively. In conclusion, isometric exercise decreases relaxation rate and increases LVEDP in patients with arterial hypertension and ventricular hypertrophy. After exercise, isovolumic relaxation remained altered suggesting the presence of stunned myocardium.

Aged↗
PubMed2005

Effects of isometric exercise on the diastolic function in patients with severe aortic stenosis with or without coronary lesion.

BACKGROUND: There is no literature evaluating the effect of exercise on patients with aortic stenosis, in which patients with and without coronary artery disease were assessed separately. OBJECTIVE: To assess the effects of isometric exercise on the diastolic function in patients with aortic stenosis (AS). METHODS: 18 patients with AS, and 5 control patients were studied (group 1, G1). Patients with AS were divided in: group 2 (G2, n=10), without coronary lesion, and group 3 (G3, n=8), with coronary lesion. All patients underwent cardiac catheterization and performed isometric exercise until heart rate increased 32+/-9%. Left ventricular systolic pressure and end diastolic pressure (LVEDP), t1/2 (relaxation index), and the +dP/dt(max) were all measured. RESULTS: The +dP/dt(max) increased in G1, G2, and G3 during exercise returning to their basal values once exercise had concluded. While exercising, the LVEDP increased in G1, G2 and G3, returning to its original baseline value only in G1 and G2. The t1/2 increased, while exercising, in G2 and G3, and continued to be elevated after the exercise in both groups although it was only statistically significant in G3. The control group did not show significant changes. CONCLUSIONS: Isometric exercise decreases relaxation rate and increases LVEDP in patients with AS. After exercise, relaxation and LVEDP remained altered only in the patients with coronary lesion. The alteration in lusitropism and increased LVEDP after exercising suggest the presence of stunned myocardium.

Aged↗
PubMed2005

Hypercholesterolemia attenuates postischemic ventricular dysfunction in the isolated rabbit heart.

The effects of the chronic administration of cholesterol on the stunned myocardium have not been studied. The objective was to determine the effect of a cholesterol enriched diet on postischemic ventricular dysfunction. In group 1 (G1, n = 7) isolated rabbit hearts underwent a follow up of ventricular function during 30 min in aerobic conditions. In group 2 (G2, n = 6) G1 was repeated but the animals were subjected to a 1% cholesterol enriched diet during 4 weeks (hypercholesterolemic animals). In group 3 (G3, n = 8) hearts underwent 15 min of global ischemia followed by 30 min of reperfusion. In Group 4 (G4, n = 11) G3 was repeated, but in hypercholesterolemic animals. Since cholesterol decreased the inotropism in basal situation, and this makes the comparison between groups difficult, we performed a Group 5 (G5, n = 7), in which G4 protocol was repeated but isoproterenol (8 microg/kg/min) was administered 10 min before ischemia, in order to match the preischemic inotropic state with respect to the normocholesterolemic ones. G1 and G2 maintained a stable inotropism during the 30 min of perfusion. The preischemic left ventricular developed pressure (LVDP) in G3 and G4 was 91.4 +/- 4.3 and 70.8 +/- 3.4 mmHg (p < 0.05), respectively, and after 30 min of reperfusion differences were not observed between G3 and G4. Nevertheless, when LVDP is expressed as a percentage, we detected an attenuation of postischemic systolic alterations in hypercholesterolemic animals (67.3 +/- 3.6 in G4 vs. 90.8 +/- 3.1% in G3, p < 0.05). When LVDP in G5 was increased until matching the one of G3, there were no differences after 30 min of reperfusion. Left ventricular end diastolic pressure increased 285 +/- 46%, 61 +/- 25% (p < 0.05 vs. G3 and G5) and 216 +/- 25% in G3, G4 and G5 at 30 min of reperfusion. There were no differences either in the values of tau or infarct size between groups. Thus, in hypercholesterolemic animals, a decrease of the preischemic inotropism exists and there is an attenuation of the stunned myocardium. When contractility of the normo and hypercholesterolemic animals is matched, the beneficial effect disappears.

Animals↗
PubMed2004

[Statement of fair retribution in medical oaths].

BACKGROUND: to determine if Medical Oaths from different times include the statement of the physician to request from patients a fair retribution for his/her medical services. METHODS: Fifty Medical Oaths found in articles and publications were analyzed. In accordance with their corresponding dates, the Oaths were grouped as ancient /medieval (12), and modern/contemporary (38). RESULTS: Of the fifty, only three specifically included the statement of fair retribution. Two of the three were medieval and belonged to the School of Medicine of Montpellier. The other text was modern (Amato Lusitano's Oath). Four writings showed statements regarding medical assistance to the poor. Eleven pledges indirectly stated that no earnings from other activities and/or relations were obtained. CONCLUSIONS: Ancient oaths emphasize fair retribution, no discrimination in medical assistance based on payment possibilities, and gain of honest earnings. Modern oaths generally do not include these topics and very few mention that the medical profession should not be exercised merely for material purposes. Despite the above, physicians should respect the limits of their obligations and should be committed to assist without discriminating, particularly without taking into consideration their patient's financial possibilities. Therefore their fees should not be excessive for the services rendered.

Codes of Ethics↗
PubMed2004

[Effects of the early administration of losartan on ventricular remodeling in rabbits with experimental myocardial infarction].

This study was carried out to investigate the effects of early administration of losartan on ventricular remodelling (VR) in rabbits with experimental myocardial infarction (MI). New Zealand rabbits underwent left coronary artery ligation. Four groups were analyzed: sham (G1; n = 13), MI (G2; n = 13), sham + Los (G3; n = 13) and MI + Los (G4; n = 13). Los (12.5 mg/kg/d) was administered 3 hours post-MI during 35 days when the animals were sacrificed. The hearts were isolated and perfused using Langendorff's technique to determine systolic and diastolic pressure-volume (P/V) curves. Hearts were weighed, fixed in formaline, cut from apex to base, and stained with Masson's trichrome and pricrosirius red. The heart weight (HW)/body weight (BW) ratio was used as an index of hypertrophy. Infarct size (IS; %), septum (SeT, mm) and scar thickness (ST, mm) were measured using morphometric analysis. Results were expressed as mean +/- SEM. IS was G2 = 25.38 +/- 5.31; G4 = 21.85 +/- 4.13 (NS). HW/BW was 3.45 +/- 0.16; 3.23 +/- 0.25; 2.87 +/- 0.16; 3.23 +/- 0.18 in G1, G2, G3 and G4, respectively. Los shifted the diastolic P/V relationship to the right in sham and MI (p < 0.05 vs sham), and did not modify the systolic relationship. Scar collagen concentration was lower in G4 (p < 0.05 vs G2). SeT was lower in G3 and G4 (p < 0.05 vs G2). In conclusion, the early administration of Los unfavorably modified post-MI-VR, increasing ventricular dilation and reducing scar collagen concentration and thickness.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2003

[Effects of isometric exercise on the diastolic function in patients with severe aortic stenosis].

The objective of the study was to determine the effects of isometric exercise on the diastolic function in patients with aortic stenosis without coronary lesion (group 1, G1, n = 9) and with coronary lesion (group 2, G2, n = 11). Patients subjected to a cardiac catheterization performed isometric exercise until their heart rate increased in 32 +/- 9% compared to baseline. The left ventricular systolic pressure, the +dP/dtmax, and the end diastolic pressure (LVEDP) were measured, and the time constant of pressure decay (tau, tau) was calculated. The +dP/dtmax increased in G1 and G2 during exercise, from a value of 1989 +/- 190 and 2428 +/- 220 mmHg/sec up to 2286 +/- 214 y 2661 +/- 230 mmHg/sec, respectively, returning afterwards to its baseline value. The LVEDP increased during exercise in G1 and G2 from a value of 30.1 +/- 2.7 and 26.5 +/- 2.2 mmHg up to 38.4 +/- 1.7 and 36.1 +/- 4.0 mmHg, respectively (p < 0.05), returning to its baseline value only in G1. The tau (tau) increased during exercise in G1 and G2 from a value of 42.8 +/- 6.8 and 44.8 +/- 4.2 m/sec up to 55.3 +/- 9.2 and 60.4 +/- 5.9 msec respectively (p < 0.05), and remained elevated after exercise in both groups although it was statistically significant only in G2. The isometric exercise decreases the relaxation rate and increases the LVEDP in patients with aortic stenosis and left ventricular hypertrophy. After exercise, relaxation remained altered in the group of patients with coronary lesion. Alteration in the lusitropism and the increase of LVEDP after exercise suggest the presence of myocardial stunning.

Aortic Valve Stenosis↗
PubMed2003

[Discrimination in medical assistance: An overview based on medical oath].

BACKGROUND: All humans have the right to receive a thorough medical attention, and should not be discriminated. AIMS: To determine if there is a significant relationship between Medical Oaths that commit to the principle of no discrimination in health care and the time, origin and source of the modifications to the Hippocratic Oath. To specify which are the conditions for no discrimination. MATERIALS AND METHODS: Fifty Oaths found in different articles and publications were analyzed and selected considering their historical context. RESULTS: Of the fifty Oaths that were analyzed, nineteen express a commitment towards no discrimination, whereas one of the texts is discriminatory. The only significant relationship found was the origin and source of the texts. The most frequently discriminating factors found are social class, religion, nationality and race. At present, other factors can be found such as ideology, moral, aptitude, sex and political and sexual preferences. CONCLUSIONS: The commitment towards no discrimination is not widely found in Medical Oaths of all times (30/50). According to the bioethics principle of justice, physicians should find the limit of their obligation as doctors in providing medical assistance to everyone alike, wealthy or poor; Christians, Hebrews or Muslims; men or women; children, adults or old; with or without infectious diseases. Non discrimination should be a vow that physicians must be willing to take despite any of the factors that could influence health care.

Health Services Accessibility↗
PubMed2003

Adenosine and cardioprotection during reperfusion--an overview.

Ischemic heart disease includes a number of entities that have been grouped in accordance with physiopathology and evolutive criteria. In recent years 'new' ischemic syndromes have been described. Within the 'new' ischemic syndromes, ventricular post-ischemic dysfunction--also known as 'stunned myocardium'--is worth mentioning. In this route, several studies have suggested that reperfusion per se could cause cellular injury (reperfusion injury). In previous years, a protective effect on the injury caused by ischemia and reperfusion in the heart has been attributed to adenosine. These effects have been documented in different experimental in vivo and in vitro models. Thus, the administration of exogenous adenosine, or agonists of adenosine receptors prior to ischemia reduces the size of the infarction, improves the recovery of the ventricular function during reperfusion (attenuating stunning) and prolongs the time period to the ischemic contracture. However, focusing on a potential therapeutic application, it is of the utmost importance to find this protection and learn the mechanisms involved when procedures are applied during early reperfusion. We showed that adenosine, administered from the beginning of reperfusion, attenuated systolic and diastolic (myocardial stiffness) alterations of the stunned myocardium. This protective effect was mediated by the activation of A1 adenosine receptors, and without modification on infarct size. According to some authors, adenosine can decrease the release of endothelin, during early reperfusion, and reduce an overload of Ca2+ that could cause a cellular lesion. Finally, ischemic preconditioning involves a series of intracellular events that are initiated with the activation of the A1 receptor, and end at the sensitive K+ ATP channels of the mitochondria. The phosphorylation and opening of these channels would cause the protective effect. Activation of this specific mechanism during reperfusion has not been studied extensively.

Adenosine↗
PubMed2003

[Diastolic behavior during postischemic hypercontraction phase in rabbit stunned myocardium].

UNLABELLED: The objective was to determine whether "hypercontraction" (HC) that occurs at the beginning of reperfusion (R) in stunned myocardium is accompanied by diastolic alterations and determine if the R with low Ca2+. Ringer's solution modifies these alterations. Isolated isovolumic rabbit hearts were divided into 2 groups. Group 1 (G1, n = 11) was perfused with Ringer's solution ([Ca2+] = 2 mM) and subjected to 15 min of global ischemia and 30 min of R. Group 2 (G2, n = 10) was R during the first 10 min with ([Ca2+] = 1 mM), which was increased to 1.5 mM and 2 mM in the perfusate at 30 min of R. The left ventricular +dP/dtmax, left ventricular end diastolic pressure (LVEDP) (stiffness index), and relaxation rate (t 1/2 and +P/-P ratio) were measured, from the beginning of R every 10 sec for 2 min, and then at 5 and 30min. At 60 sec of R the +dP/dtmax in G1 was increased (76.88 +/- 5.37% vs preischemic value) and was attenuated in G2 (48.22 +/- 3.40%; P < 0.05 vs G1). The LVEDP in G1 was increased early in the R, although it was negatively correlated with HC degree (r = .0.7477; p = 0.008). This increase was attenuated in G2 (P < 0.05 vs G1) at 60 sec R. There was a dealy in the relaxation at 60 secR in both group (G1 vs G2, NS). IN CONCLUSION: HC is accompanied by diastolic alterations. The improvement of HC is inversely related with LVEDP. During R the stiffness during the relaxation rate was normal. The R with low Ca2+ attenuated the HC and the diastolic stiffness.

Animals↗
PubMed2002

Xanthine oxidase contributes to preconditioning's preservation of left ventricular developed pressure in isolated rat heart: developed pressure may not be an appropriate end-point for studies of preconditioning.

Studies of preconditioning frequently use the isolated rat heart model in which recovery of post-ischemic function is the end-point. However, function following an episode of ischemia/reperfusion represents a composite of both stunning, which is related to free radical production and is not attenuated by preconditioning, and tissue salvage, the primary effect of preconditioning. Brief ischemia/reperfusion is also known to diminish adenosine release during subsequent ischemia by a mechanism independent of preconditioning's anti-infarct effect. Reduced purine release would diminish generation of free radicals by xanthine oxidase in rat heart and thus produce less stunning. In this paradigm preserved post-ischemic function in rat heart might look similar to salvage by preconditioning, but its mechanism would be quite different and not be relevant to the xanthine oxidase-deficient human heart. This hypothesis was tested in isolated rat hearts. Control or ischemically preconditioned hearts were subjected to 30 min of global ischemia and 60 min of reperfusion, either in the presence or absence of 25 micromol/l allopurinol, an inhibitor of xanthine oxidase. In non-preconditioned hearts allopurinol increased left ventricular developed pressure after 60 min of reperfusion from 26 +/- 5 mmHg in control hearts to 47 +/- 7 mmHg, whereas developed pressure in preconditioned hearts following reperfusion was 59 +/- 5 mmHg and was unaffected by allopurinol. Developed pressure in non-preconditioned hearts treated with allopurinol was midway between that for untreated control and preconditioned hearts suggesting that at least 50% of the recovery of developed pressure in preconditioned hearts may be related to free radical-induced stunning. In xanthine oxidase-deficient rabbit hearts, return of function was not different between non-preconditioned and preconditioned hearts. Therefore, post-ischemic developed pressure in the rat is significantly affected by purine-dependent stunning, and, hence, may be an unreliable marker of tissue salvage and also a poor index of what might be cardioprotective in man.

Allopurinol↗
PubMedDate not supplied

Effects of the early administration of losartan on the functional and morphological aspects of postmyocardial infarction ventricular remodeling in rabbits.

BACKGROUND: The effects of losartan (Los) on ventricular remodeling (VR) remain controversial. The objective was to determine whether early administration of Los to rabbits with myocardial infarction (MI) modifies VR. METHODS: New Zealand rabbits underwent left coronary artery ligation. Four groups were analyzed: Sham (G(1); n = 13), MI (G(2); n = 13), Sham+Los (G(3); n = 13), and MI+Los (G(4); n = 13). Los (12.5 mg/kg/day) was administered from 3 h post-MI and during 35 days. At the end of the protocol, the hearts were isolated and perfused to determine pressure-volume curves (P/V). Hearts were weighed, cut, and stained with picrosirius red. The heart weight (HW)/body weight (BW) ratio was determined. Infarct size (IS;%), septum (SeT, mm) and scar thickness (ST, mm), myocyte area (microm(2)), and width (mum) were measured. RESULTS (X +/- S.E.M.): Los shifted the diastolic left ventricular (LV) P/V relationship to the right in sham and MI (P < .05 vs. sham), with no changes in the systolic relation. IS was G(2) = 25.38 +/- 5.31 and G(4) = 21.85 +/- 4.13 (NS); HW/BW was 0.34+/-0.01, 0.35 +/- 0.02, 0.29 +/- 0.02 (P < .05 vs. G(1) and G(2)), and 0.32 +/- 0.02 in G(1), G(2), G(3), and G(4), respectively. Scar collagen concentration (%) was lower in G(4) (P < .05 vs. G(2)). SeT was lower in G(3) and G(4) (P < .05 vs. G(2)). The width and area of the septum myocytes increased in the untreated infarct, and Los suppressed that increase. CONCLUSION: The early administration of Los unfavorably modified post-MI VR, increasing ventricular dilation, reducing scar collagen concentration and thickness, and inhibiting myocytes width and area increase. The dilation observed in sham animals' hearts suggests that infarct was not the main factor in the dilation of the cavity.

Angiotensin II Type 1 Receptor Blockers↗
PubMedDate not supplied

Histopathologic time course of myocardial infarct in rabbit hearts.

INTRODUCTION: The histopathologic evolution of myocardial infarct and of remote zones in rabbit hearts was studied. METHODS: The left coronary artery of 55 rabbits was ligated and rabbits were sacrificed at 2, 4, 6, 8, 12, 14, 16, 18, 26, 35 and 56 days post-ligature (n=5 per group). Two rabbits were used as control and four were sham-operated. The hearts were excised, cut in slices and stained with hematoxylin-eosin, Masson's trichrome and picrosirius red. The histological evaluation was semiquantitative (scale: 0 to ++). RESULTS: At day 2, the presence of neutrophils was ++, decreasing suddenly at day 4 and disappearing completely at day 6. The proliferation of cells with features of fibroblasts increased from days 4 to 14 post-occlusion. Coagulation necrosis in mid-myocardium during the first week was ++. Subendocardial myocytolysis was evident from day 2 up to day 56 post-infarction. During the second week, proliferation of lymphocytes and macrophages (++), granulation tissue formation (++) and incipient traces of fibrosis that peaked at day 35 were observed. Scarring was complete at day 56 (++). In remote zones (right ventricle and septum), the proliferation of cells+ on Vimentin was observed at day 2, and perivascular, interstitial and endocardial fibrosis started to increase at day 6 and peaked at day 16. CONCLUSION: Although myocardial infarction in rabbits maintains the essence of the infarct chronology, some differences as the early presence of cells+ on Vimentin and subendocardial fibrosis in infarcted areas, and also the rapid increase and early disappearance of neutrophils appear when other species are considered. An interesting finding was the early proliferation of cells with features of fibroblasts in remote zones.

Animals↗