RESUMO
BACKGROUND: Recurrent airway obstruction (RAO) is common in horses. Although pulmonary artery (PA) pressure increases during RAO, cardiac function in horses with RAO has received limited attention. HYPOTHESIS: The purpose of this study was to noninvasively determine the cardiovascular effects of acute pulmonary obstruction (APO) in horses with RAO and their reversibility. ANIMALS: Five geldings with RAO, inducible by exposure to moldy hay, were studied. METHODS: Pulmonary mechanics, echocardiography, serum troponin I concentrations, arterial blood gases, and hematocrit were obtained before and after 7 days of APO. Heart rate, PA diameter and flow characteristics, right and left ventricular luminal dimensions and wall thicknesses, global cardiac performance, and evidence of myocardial damage were evaluated. Pulmonary mechanics and echocardiography were reevaluated during remission. RESULTS: [corrected] Severe, transient APO did not induce chronic cor pulmonale in horses, because cardiac anatomy and function were normal between episodes. An acute episode of APO produced anatomical and functional cardiac changes in both the right and left heart (including increased PA diameter, abnormal septal motion, and decreased left ventricular diameter and estimated stroke volume), possibly because of the development of pulmonary hypertension, without apparent myocardial damage. The decrease in stroke volume was offset by the increase in heart rate. CONCLUSIONS AND CLINICAL IMPORTANCE: With APO of 7 days' duration, cardiovascular abnormalities and the functional airway changes that produce them are reversible when the offending allergens are removed.
Assuntos
Cardiopatias/veterinária , Doenças dos Cavalos/etiologia , Pneumopatias Obstrutivas/veterinária , Animais , Ecocardiografia/veterinária , Cardiopatias/sangue , Cardiopatias/etiologia , Doenças dos Cavalos/sangue , Cavalos , Pneumopatias Obstrutivas/sangue , Pneumopatias Obstrutivas/complicações , Masculino , Troponina I/sangueRESUMO
Preexistent cardiopulmonary disease in humans appears to enhance susceptibility to the adverse effects of ambient particulate matter. Previous studies in this laboratory have demonstrated enhanced inflammation and mortality after intratracheal instillation (IT) and inhalation (INH) of residual oil fly ash (ROFA) in a rat model of pulmonary hypertension induced by monocrotaline (MCT). The present study was conducted to examine the effects of ROFA in this model on ventilatory function in unanesthetized, unrestrained animals. Sixty-day-old male CD rats were injected with MCT (60 mg/kg) or vehicle (VEH) intraperitoneally 10 days before IT of ROFA (8.3 mg/kg) or saline (SAL) (control) or nose-only INH of ROFA [15 mg/m3 for 6 hr on 3 consecutive days or air (control)]. At 24 and 72 hr after exposure, rats were studied individually in a simultaneous gas uptake/whole-body plethysmograph. Lungs were removed at 72 hr for histology. Pulmonary test results showed that tidal volume (VT) decreased 24 hr after IT of ROFA in MCT-treated rats. Breathing frequency, minute volume (VE), and the ventilatory equivalent for oxygen increased in MCT- and VEH-treated rats 24 hr after IT or INH of ROFA and remained elevated 72 hr post-IT. O2 uptake (VO2) decreased after IT of ROFA in MCT-treated rats. Carbon monoxide uptake decreased 24 hr after IT of ROFA, returning to control values in VEH-treated rats but remaining low in MCT-treated rats 72 hr post-IT. ROFA exposure induced histologic changes and abnormalities in several ventilatory parameters, many of which were enhanced by MCT treatment.
Assuntos
Carbono/toxicidade , Hipertensão Pulmonar/complicações , Exposição por Inalação , Pulmão/patologia , Animais , Carbono/administração & dosagem , Cinza de Carvão , Modelos Animais de Doenças , Inflamação , Pulmão/fisiologia , Masculino , Monocrotalina/administração & dosagem , Tamanho da Partícula , Material Particulado , Ratos , Ratos Sprague-Dawley , Testes de Função Respiratória/veterináriaRESUMO
The pharmacokinetics of enalapril (0.5 mg/kg i.v.) and the pharmacodynamics of enalapril (0.5 mg/kg PO) in 5 mares were investigated. After single i.v. dosing, concentrations of enalapril and enalaprilat, its active metabolite, were measured. Two weeks later, enalapril was administered by nasogastric tube. Potassium, creatinine, blood urea nitrogen (BUN), enalapril, and enalaprilat concentrations and angiotensin converting enzyme (ACE) activity were measured in serum. In addition, heart rate, blood pressure, digital venous blood gases, and lactate were measured. Two weeks later, enalapril was again administered by nasogastric tube. To mimic activation of the renin-angiotensin-aldosterone system, angiotensin I (0.5 microg/kg) was administered at fixed intervals, followed by blood-pressure and heart-rate measurement. The elimination half lives of enalapril and enalaprilat were 0.59 and 1.25 hours, respectively, after i.v. administration. After PO administration, enalapril and enalaprilat were not detectable in serum. There was a tendency (P = .0625) toward a decrease in ACE activity 45-120 minutes after enalapril administration, but ACE activity suppression was never > 16%. There was a tendency (P = .0625) toward a decrease in mean arterial pressure (MAP) 6-8 hours after enalapril administration. Serum concentrations of potassium, creatinine, and BUN and digital venous blood gases and lactate concentrations did not change. In response to angiotensin I, there was a tendency (P = .0625) toward a decrease in the MAP response 4-24 hours after enalapril administration. Single-dose enalapril at 0.5 mg/kg PO did not demonstrate significant availability, pharmacodynamic effect, or substantial suppression of ACE activity.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacocinética , Enalapril/farmacocinética , Enalaprilato/farmacocinética , Cavalos/metabolismo , Administração Oral , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/sangue , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Área Sob a Curva , Análise Química do Sangue/veterinária , Gasometria/veterinária , Pressão Sanguínea/efeitos dos fármacos , Enalapril/administração & dosagem , Enalapril/sangue , Enalapril/farmacologia , Enalaprilato/administração & dosagem , Enalaprilato/sangue , Feminino , Frequência Cardíaca/efeitos dos fármacos , Infusões Intravenosas/veterinária , Peptidil Dipeptidase A/efeitos dos fármacosRESUMO
This study was initiated to identify the signalment and clinical variables potentially associated with hypomagnesemia in horses evaluated at the North Carolina State University, College of Veterinary Medicine (NCSU-CVM) veterinary teaching hospital between January 1999 and May 2001. A nested case reference study (nested case-control study) was conducted to examine the potential relationship between hypomagnesemia and signalment, serum chemistry panel analyses, number of hospitalization days, discharge status, and diagnosis. A series of independent and multivariable logistic regression models were used to assess the potential association of each variable with low total serum magnesium concentrations. Four hundred one of 823 (48.7%) horses had serum total magnesium concentrations below the normal reference range. Hypomagnesemia was more likely to occur in horses older than I month of age. Colic (odds ratio [OR]: 2.96, 95% confidence intervals [CI]: 2.14-4.08), acute diarrhea (OR: 5.91, 95% CI: 2.32-15.06), other gastrointestinal disease (OR: 2.07, 95% CI: 1.15-3.71), infectious respiratory disease (OR: 5.07, 95% CI: 2.09-12.28), and multiorgan system disease (OR: 2.31, 95% CI: 1.24-4.28) were associated with hypomagnesemia in adult horses, whereas foals with diarrhea (excluding septic foals) (OR: 0.11, 95% CI: 0.01-0.84) were less likely to have hypomagnesemia. Overall, there was no relationship between hypomagnesemia and mortality (OR: 1.00, 95% CI: 0.72-1.41), but horses with colic and hypomagnesemia were less likely to die than horses with colic and normal or high total magnesium (OR: 0.53, 95% CI: 0.30-0.95). Among horses that survived, hypomagnesemia at admission was associated with a longer hospitalization period (OR: 1.45, 95% CI: 1.00-2.11).
Assuntos
Doenças dos Cavalos/sangue , Deficiência de Magnésio/veterinária , Animais , Análise Química do Sangue/veterinária , Estudos de Casos e Controles , Feminino , Cavalos , Hospitalização , Magnésio/sangue , Deficiência de Magnésio/sangue , Masculino , Análise de RegressãoRESUMO
Continuous rate infusion (CRI) of furosemide in humans is considered superior to intermittent administration (IA). This study examined whether furosemide CRI, compared with IA, would increase diuretic efficacy with decreased fluid and electrolyte fluctuations and activation of the renin-angiotensin-aldosterone system (RAAS) in the horse. Five mares were used in a crossover-design study. During a 24-hour period, each horse received a total of 3 mg/kg furosemide by either CRI (0.12 mg/kg/h preceded by a loading dose of 0.12 mg/kg IV) or IA (1 mg/kg IV q8h). There was not a statistically significant difference in urine volume over 24 hours between methods; however, urine volume was significantly greater after CRI compared with IA during the first 8 hours ([median 25th percentile, 75th percentile]: 9.6 L [8.9, 14.4] for CRI versus 5.9 L [5.3, 6.0] for IA). CRI produced a more uniform urine flow, decreased fluctuations in plasma volume, and suppressed renal concentrating ability throughout the infusion period. Potassium, Ca, and Cl excretion was greater during CRI than IA (1,133 mmol [1.110, 1,229] versus 764 mmol [709, 904], 102.7 mmol [96.0, 117.2] versus 73.3 mmol [65.0, 73.5], and 1,776 mmol [1,657, 2.378] versus 1,596 mmol [1,457, 1,767], respectively). Elimination half-lives of furosemide were 1.35 and 0.47 hours for CRI and IA, respectively. The area under the excretion rate curve was 1,285.7 and 184.2 mL x mg/mL for CRI and IA, respectively. Furosemide CRI (0.12 mg/kg/h) for 8 hours, preceded by a loading dose (0.12 mg/kg), is recommended when profound diuresis is needed acutely in horses.
Assuntos
Diuréticos/administração & dosagem , Furosemida/administração & dosagem , Cavalos/fisiologia , Animais , Cálcio/urina , Cloretos/urina , Estudos Cross-Over , Diuréticos/sangue , Diuréticos/farmacocinética , Diuréticos/urina , Feminino , Furosemida/sangue , Furosemida/farmacocinética , Furosemida/urina , Cavalos/sangue , Cavalos/urina , Infusões Intravenosas , Volume Plasmático/efeitos dos fármacos , Volume Plasmático/fisiologia , Potássio/urina , Sistema Renina-Angiotensina/efeitos dos fármacos , Gravidade Específica/efeitos dos fármacosRESUMO
Furosemide is the most common diuretic drug used in horses. Furosemide is routinely administered as IV or IM bolus doses 3-4 times a day. Administration PO is often suggested as an alternative, even though documentation of absorption and efficacy in horses is lacking. This study was carried out in a randomized, crossover design and compared 8-hour urine volume among control horses that received placebo, horses that received furosemide at 1 mg/kg PO, and horses that received furosemide at 1 mg/kg IV. Blood samples for analysis of plasma furosemide concentrations, PCV, and total solids were obtained at specific time points from treated horses. Furosemide concentrations were determined by reversed-phase high-performance liquid chromatography with fluorescent detection. Systemic availability of furosemide PO was poor, erratic, and variable among horses. Median systemic bioavailability was 5.4% (25th percentile, 75th percentile: 3.5, 9.6). Horses that received furosemide IV produced 7.4 L (7.1, 7.7) of urine over the 8-hour period. The maximum plasma concentration of 0.03 microg/mL after administration PO was not sufficient to increase urine volume compared with control horses (1.2 L [1.0, 1.4] PO versus 1.2 L [1.0, 1.4] control). There was a mild decrease in urine specific gravity within 1-2 hours after administration of furosemide PO, and urine specific gravity was significantly lower in horses treated with furosemide PO compared with control horses at the 2-hour time point. Systemic availability of furosemide PO was poor and variable. Furosemide at 1 mg/kg PO did not induce diuresis in horses.
Assuntos
Diuréticos/farmacologia , Diuréticos/farmacocinética , Furosemida/farmacologia , Furosemida/farmacocinética , Cavalos/metabolismo , Administração Oral , Animais , Disponibilidade Biológica , Cromatografia Líquida de Alta Pressão/veterinária , Feminino , Injeções Intravenosas/veterinária , Gravidade Específica/efeitos dos fármacos , Resultado do TratamentoRESUMO
OBJECTIVE: To identify clinical signs, underlying cardiac conditions, echocardiographic findings, and prognosis for horses with congestive heart failure. DESIGN: Retrospective study. ANIMALS: 14 horses. PROCEDURE: Signalment; history; clinical signs; clinicopathologic, echocardiographic, and radiographic findings; treatment; and outcome were determined by reviewing medical records. RESULTS: All 14 horses were examined because of a heart murmur; tachycardia was identified in all 14. Twelve horses had echocardiographic evidence of enlargement of 1 or more chambers of the heart. Other common clinical findings included jugular distention or pulsation, crackles, cough, tachypnea, and ventral edema. Nine horses had signs consistent with heart failure for > 6 days. Underlying causes for heart failure included congenital defects, traumatic vascular rupture, pericarditis, pulmonary hypertension secondary to heaves, and valvular dysplasia. Seven horses were euthanatized after diagnosis of heart failure; 5 were discharged but were euthanatized or died of complications of heart disease within 1 year after discharge. The remaining 2 horses were discharged but lost to follow-up. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that congestive heart failure is rare in horses. A loud heart murmur accompanied by either jugular distention or pulsation, tachycardia, respiratory abnormalities (crackles, cough, tachypnea), and ventral edema were the most common clinical signs. Echocardiography was useful in determining the underlying cause in affected horses. The long-term prognosis for horses with congestive heart failure was grave.
Assuntos
Insuficiência Cardíaca/veterinária , Doenças dos Cavalos/diagnóstico , Doenças dos Cavalos/terapia , Animais , Ecocardiografia/veterinária , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/terapia , Doenças dos Cavalos/mortalidade , Cavalos , Masculino , Prognóstico , Estudos Retrospectivos , Taquicardia/diagnóstico , Taquicardia/terapia , Taquicardia/veterinária , Resultado do TratamentoRESUMO
OBJECTIVES: One potential method of evaluating renin-angiotensin-aldosterone system (RAAS) activation involves the quantification of urinary aldosterone excretion. While blood concentrations of aldosterone are easily obtained, results may be misleading because of minute-to-minute variation in aldosterone secretion and subsequent blood concentrations. Urinary aldosterone concentration measurement represents a more consistent "pooled" index of aldosterone secretion, but obtaining 24-h urine samples is time-consuming, difficult, and fraught with potential error. We postulated that the urinary aldosterone:creatinine ratio, measured from spot urine samples, would correlate well with 24-h urinary aldosterone excretion, and would provide a simple index of aldosterone excretion that would eliminate the need for 24-h urine collection. ANIMALS, MATERIALS AND METHODS: After validating an assay for aldosterone in canine urine, 24-h urinary aldosterone excretion was determined by radioimmunoassay from 8 normal, male beagle dogs under control conditions, after RAAS stimulation with amlodipine administration, and after RAAS attenuation with the addition of enalapril to amlodipine administration. Spot urine samples, each obtained at the same time of day, were used to determine the aldosterone:creatinine ratio during control conditions, RAAS stimulation, and RAAS attenuation. RESULTS: The aldosterone:creatinine ratio from spot-checked urine samples correlated well with 24-h urinary aldosterone excretion (r=0.77, P<0.0001). CONCLUSIONS: A spot urinary aldosterone:creatinine ratio might be substituted for 24-h urinary aldosterone determination.