Objective--To study whether end products of 2 pathways of anaerobic energy metabolism, lactate and purines, that accumulate in the blood after intense exercise indicate any relation to exercise performance. Design--Venous blood samples were taken within 1 and 15 minutes after a trotting race of 2,100 m. Animals--16 Clinically healthy Standardbred trotters. Procedure--Blood and plasma lactate concentrations were measured by enzymatic analyzer, and purines, uric acid and allantoin, were determined by high-performance liquid chromatography. The concentrations of metabolites were then correlated to racing time and individual performance indexes that are annually calculated from the percentage of winnings, placings, and starts rejected, average earnings per start, and the racing record. Results--Blood lactate concentration immediately and calculated cell lactate concentration immediately and 15 minutes after the race correlated positively (P < 0.05 to P < 0.01 ) with the individual performance indexes. Plasma lactate concentration was not correlated to the individual performance indexes. Uric acid concentration, immediately and 15 minutes after the race, was negatively correlated (P < 0.05) to the individual performance indexes, and a positive relation (P < 0.05) was found between the highest concentration of uric acid and the racing time. Concentration of allantoin immediately or 15 minutes after the race did not have any significant correlation to the individual performance indexes. Conclusions--Accumulation of lactate in the blood, which was greater in the superior performing horses, may prove to be an useful predictor of anaerobic capacity. The results also indicate that the loss of purine nucleotides was less in the superior performing horses, although further studies are needed to confirm this.

Objective--To study whether end products of 2 pathways of anaerobic energy metabolism, lactate and purines, that accumulate in the blood after intense exercise indicate any relation to exercise performance. Design--Venous blood samples were taken within 1 and 15 minutes after a trotting race of 2,100 m. Animals--16 Clinically healthy Standardbred trotters. Procedure--Blood and plasma lactate concentrations were measured by enzymatic analyzer, and purines, uric acid and allantoin, were determined by high-performance liquid chromatography. The concentrations of metabolites were then correlated to racing time and individual performance indexes that are annually calculated from the percentage of winnings, placings, and starts rejected, average earnings per start, and the racing record. Results--Blood lactate concentration immediately and calculated cell lactate concentration immediately and 15 minutes after the race correlated positively (P < 0.05 to P < 0.01) with the individual performance indexes. Plasma lactate concentration was not correlated to the individual performance indexes. Uric acid concentration, immediately and 15 minutes after the race, was negatively correlated (P < 0.05) to the individual performance indexes, and a positive relation (P < 0.05) was found between the highest concentration of uric acid and the racing time. Concentration of allantoin immediately or 15 minutes after the race did not have any significant correlation to the individual performance indexes. Conclusions--Accumulation of lactate in the blood, which was greater in the superior performing horses, may prove to be an useful predictor of anaerobic capacity. The results also indicate that the loss of purine nucleotides was less in the superior performing horses, although further studies are needed to confirm this.

Investigation of the structure of equine articular cartilage link protein (LP) from individuals ranging in age from 1 to 15 years identified 3 distinct isoforms having molecular weights of 46,000, 43,000, and 41,000. The relative amounts of each of the 3 isoforms altered with age. The largest form did not change with age; however, amounts of the Mr 43,000 and 41,000 forms increased with increasing age. The results suggested that an accumulation, in the extracellular matrix of cartilage, of these 2 smaller products may have arisen from proteolytic cleavage. The complete amino acid sequence of the protein core was determined from complementary DNA products prepared by polymerase chain reaction amplification of cartilage LP mRNA. The sequence had 96% similarity with human LP and with that of other species for which the primary structure has been determined. This high degree of sequence conservation and the isoform data indicate that extracellular processing of LP occurs by similar mechanisms in various species. At the transcription level, equine chondrocytes were found to express LP as 2 abundant mRNA of 5.0 and 3.0 kb, and a smaller mRNA of 1.5 kb. Processing of the LP mRNA in horses, thus, appears to be similar to that found in other species investigated, and although multiple transcripts are present, the coding region remains unaltered and only 1 protein product is made.

Investigation of the structure of equine articular cartilage link protein (LP) from individuals ranging in age from 1 to 15 years identified 3 distinct isoforms having molecular weights of 46,000, 43,000, and 41,000. The relative amounts of each of the 3 isoforms altered with age. The largest form did not change with age; however, amounts of the Mr 43,000 and 41,000 forms increased with increasing age. The results suggested that an accumulation, in the extracellular matrix of cartilage, of these 2 smaller products may have arisen from proteolytic cleavage. The complete amino acid sequence of the protein core was determined from complementary DNA products prepared by polymerase chain reaction amplification of cartilage LP mRNA. The sequence had 96% similarity with human LP and with that of other species for which the primary structure has been determined. This high degree of sequence conservation and the isoform data indicate that extracellular processing of LP occurs by similar mechanisms in various species. At the transcription level, equine chondrocytes were found to express LP as 2 abundant mRNA of 5.0 and 3.0 kb, and a smaller mRNA of 1.5 kb. Processing of the LP mRNA in horses, thus, appears to be similar to that found in other species investigated, and although multiple transcripts are present, the coding region remains unaltered and only 1 protein product is made.

We evaluated the pharmacokinetics of IV administered sodium heparin and the pharmacodynamic effect of heparin on lipoprotein lipase (LPL) activity Horses were allotted to 3 groups. Plasma samples were obtained from each horse before and at various times for 6 hours after heparin administration for determination of heparin concentration, LPL activity, and activated partial thromboplastin time (APTT). The disposition of heparin was dose dependent. The area under the plasma heparin concentration vs time curve (AUC) increased more than proportionally with dose, indicating that heparin elimination was nonlinear. Total clearance of heparin was similar after the 40 and 80 IU/kg of body weight dosages, averaging 0.45 and 0.36 IU/kg/min, respectively. However, after administration of the 120 IU/kg dose, clearance was significantly less than that after the 40 IU/kg dose. The half-life of heparin averaged 53, 70, and 136 minutes after 40, 80, and 120 IU/kg, respectively, with significant differences observed between the low and high doses. In contrast to heparin, the area under the plasma concentration vs time curve for LPL activity increased less than proportionally with dose. Maximal LPL activity observed was independent of dose, averaging 4.8 micromole of free fatty acids/ml/h. The APTT was significantly prolonged for 120 minutes after administration of the 40 IU/kg dose. Correlation coefficients for LPL activity vs either plasma heparin concentration or APTT were less than 0.7, indicating that neither laboratory measure can be used to accurately predict plasma LPL activity.

We evaluated the pharmacokinetics of IV administered sodium heparin and the pharmacodynamic effect of heparin on lipoprotein lipase (LPL) activity Horses were allotted to 3 groups. Plasma samples were obtained from each horse before and at various times for 6 hours after heparin administration for determination of heparin concentration, LPL activity, and activated partial thromboplastin time (APTT). The disposition of heparin was dose dependent. The area under the plasma heparin concentration vs time curve (AUC) increased more than proportionally with dose, indicating that heparin elimination was nonlinear. Total clearance of heparin was similar after the 40 and 80 IU/kg of body weight dosages, averaging 0.45 and 0.36 IU/kg/min, respectively. However, after administration of the 120 IU/kg dose, clearance was significantly less than that after the 40 IU/kg dose. The half-life of heparin averaged 53, 70, and 136 minutes after 40, 80, and 120 IU/kg, respectively, with significant differences observed between the low and high doses. In contrast to heparin, the area under the plasma concentration vs time curve for LPL activity increased less than proportionally with dose. Maximal LPL activity observed was independent of dose, averaging 4.8 micromole of free fatty acids/ml/h. The APTT was significantly prolonged for 120 minutes after administration of the 40 IU/kg dose. Correlation coefficients for LPL activity vs either plasma heparin concentration or APTT were less than 0.7, indicating that neither laboratory measure can be used to accurately predict plasma LPL activity.

We compared the ability of 2 alpha2-adrenergic receptor antagonists, atipamezole and yohimbine, to reverse medetomidine-induced CNS depression and cardiorespiratory changes in lambs. Twenty lambs (7.8 +/- 2.6 kg) were randomly allotted to 4 treatment groups (n = 5). Each lamb was given medetomidine (30 micrograms/kg of body weight, IV), followed in 15 minutes by IV administration of atipamezole (30 or 60 micrograms/kg), yohimbine (1 mg/kg), or 0.9% NaCl (saline) solution. Medetomidine caused lateral recumbency in 1 to 2 minutes in all treated lambs. Medetomidine significantly (P < 0.05) decreased heart rate at 5 and 10 minutes after its administration. Heart rate remained above 120 beats/min, and severe bradycardia (< 70 beats/min) and other arrhythmias did not occur throughout the study. Medetomidine also induced tachypnea in all treated lambs. The tachypnea was abolished by atipamezole and yohimbine, but not by saline solution administration. The medetomidine-induced tachypnea did not significantly affect arterial pH and PaCO2. Arterial oxygen tension was within acceptable range (PaO2 = 71 to 62 mm of Hg), but was lower than expected. Administration of atipamezole, yohimbine, or saline solution did not change PaO2 significantly. Lambs treated with 30 or 60 micrograms of atipamezole/kg were able to walk unassisted in 2.4 +/- 0.4 and 2.3 +/- 0.7 minutes, respectively, whereas yohimbine-and saline-treated lambs did not walk unassisted until 15.6 +/- 2.7 and 73.0 +/- 6.8 minutes later, respectively. Results of this study indicated that medetomidine is a potent CNS depressant in lambs. Atipamezole at dosage of 30 or 60 micrograms/kg was equally effective, and was more effective in antagonizing medetomidine-induced CNS depression than was yohimbine.

We compared the ability of 2 alpha2-adrenergic receptor antagonists, atipamezole and yohimbine, to reverse medetomidine-induced CNS depression and cardiorespiratory changes in lambs. Twenty lambs (7.8 +/- 2.6 kg) were randomly allotted to 4 treatment groups (n = 5). Each lamb was given medetomidine (30 micrograms/kg of body weight, IV), followed in 15 minutes by IV administration of atipamezole (30 or 60 micrograms/kg), yohimbine (1 mg/kg), or 0.9% NaCl (saline) solution. Medetomidine caused lateral recumbency in 1 to 2 minutes in all treated lambs. Medetomidine significantly (P < 0.05) decreased heart rate at 5 and 10 minutes after its administration. Heart rate remained above 120 beats/min, and severe bradycardia (< 70 beats/min) and other arrhythmias did not occur throughout the study. Medetomidine also induced tachypnea in all treated lambs. The tachypnea was abolished by atipamezole and yohimbine, but not by saline solution administration. The medetomidine-induced tachypnea did not significantly affect arterial pH and PaCO2. Arterial oxygen tension was within acceptable range (PaO2 = 71 to 62 mm of Hg), but was lower than expected. Administration of atipamezole, yohimbine, or saline solution did not change PaO2 significantly. Lambs treated with 30 or 60 micrograms of atipamezole/kg were able to walk unassisted in 2.4 +/- 0.4 and 2.3 +/- 0.7 minutes, respectively, whereas yohimbine- and saline-treated lambs did not walk unassisted until 15.6 +/- 2.7 and 73.0 +/- 6.8 minutes later, respectively. Results of this study indicated that medetomidine is a potent CNS depressant in lambs. Atipamezole at dosage of 30 or 60 micrograms/kg was equally effective, and was more effective in antagonizing medetomidine-induced CNS depression than was yohimbine.

Cytologic examination of bronchoalveolar lavage fluid (BALF), including phenotypic analysis of lymphocytes, was performed on 32 Standardbreds with poor race performance and endoscopic examination findings characteristic of inflammatory airway disease (IAD). Nucleated cell counts in BALF from IAD-affected horses were higher than those in control horses; the cytologic profile of BALF in affected horses included mixed inflammation, characterized by mild neutrophilia, lymphocytosis, and monocytosis. Eosinophil and mast cell counts were not higher in the IAD-affected group, compared with those in the control group; however, 4 IAD-affected horses had marked eosinophilia (24.7 +/- 4.8% SEM) in BALF. Phenotypic analysis of lymphocytes in BALF obtained from IAD-affected horses revealed a low proportion of CD4-positive cells and B cells, compared with those in the control group; these findings may have been representative of a greater proportion of non-B, non-T cells (null cells) in horses with IAD. The cytologic profile of BALF obtained from horses with IAD differed from that in horses affected with chronic obstructive pulmonary disease, suggesting that the pathogenesis of inflammation in horses with IAD may differ from that of chronic obstructive pulmonary disease.

Cytologic examination of bronchoalveolar lavage fluid (BALF), including phenotypic analysis of lymphocytes, was performed on 32 Standardbreds with poor race performance and endoscopic examination findings characteristic of inflammatory airway disease (IAD). Nucleated cell counts in BALF from IAD-affected horses were higher than those in control horses; the cytologic profile of BALF in affected horses included mixed inflammation, characterized by mild neutrophilia, lymphocytosis, and monocytosis. Eosinophil and mast cell counts were not higher in the IAD-affected group, compared with those in the control group; however, 4 IAD-affected horses had marked eosinophilia (24.7 +/- 4.8% SEM) in BALF. Phenotypic analysis of lymphocytes in BALF obtained from IAD-affected horses revealed a low proportion of CD4-positive cells and B cells, compared with those in the control group; these findings may have been representative of a greater proportion of non-B, non-T cells (null cells) in horses with IAD. The cytologic profile of BALF obtained from horses with IAD differed from that in horses affected with chronic obstructive pulmonary disease, suggesting that the pathogenesis of inflammation in horses with IAD may differ from that of chronic obstructive pulmonary disease.