Transcript Electrical Inhibition (EI) of Human Preterm Uterine Contractions

Electrical Inhibition (EI)
Of
Human Preterm Uterine Contractions:
Just Another Pretty Smooth Muscle!
Jeffrey Karsdon, M.D.; Neonatology, Lambda Max, Baldwin, NY, USA
Graham G. Ashmead, M.D.; OBGYN, St. Luke’s-Roosevelt Hospital Center, New York, NY, USA
Manal El Daouk, M.D.; OBGYN, St. Luke’s-Roosevelt Hospital Center, New York, NY, USA
William M. Huang, M.D.; OBGYN, New York Downtown Hospital, New York, NY, USA
Hypothesis: Electrical pacemaker will decrease smooth muscle contractions or tone.
Electroceutical therapy or Electrical Inhibition (EI).
Background: Smooth muscles produce
A
contractions or tone e.g. preterm uterine
contractions or vascular tone (blood flow).
Pharmaceuticals do not control
smooth muscles efficiently and have
many side effects.
EI of electrical (EMG) activity does
B
efficiently control smooth muscle
contractions or tone with few side effects:
A. Human uterine smooth muscle,
increased spontaneous EMG activity
precedes contractions (top,
contractions; bottom, EMG).
B. Human corpus cavernosum smooth
muscle, decreased spontaneous EMG C
activity (arrows) decreased smooth
muscle tone allowing increased blood
flow (top, blood flow; bottom, EMG).
C. Rat uterine smooth muscle, electrical
inhibition (EI) of spontaneous EMG
(arrows) decreases contractions and
tone (top, contractions; bottom, EMG).
Wolfs et. al. Obstet Gynecol. 1971;37:241-246
Jiang et. al. J Urol. 2005;174:1917-1920
Karsdon (unpublished)
Method: EI pacemaker/generator sends the electrical current to an electrode
catheter that is placed next to the smooth muscle of the cervix.
A. EI generator:
A.
1. Power cable
2. Step down transformer
3. Power connector cable
4. EI generator with connector
5. Electrode catheter connector cable
6. Electrode catheter
B. Electrodes directly onto the uterus.
C. Transvaginal electrode catheter (TVC)
placed into the vaginal canal with the tip
next to the smooth muscle of the rat cervix.
1 2 3
4
5
D. TVC placed into the vaginal canal with the
tip next to the smooth muscle of the human
cervix (arrow).
D.
C.
6
B.
Method: Outcomes
Uterine smooth muscle contraction
or tone measurements:
1) rabbit and rat, intrauterine pressure
(IUP);
2) rat, EMG and pup birth intervals (BI);
3) human, uterine contractions
(tocodynomometer/toco) and fetal
heart rate (FHR) for side effects.
Results:
A.
A. EI in the rat decreased EMG activity
(spectrum analysis):
1. amplitude
2. spike frequency
3. area-under-the-curve or power
B. EI decreased the EMG dependent smooth
muscle tone and contractions, both
B.
amplitude and frequency, in all species
studied;
top panel: rabbit, EI (arrow up)
decreased IUP only in the study horn and
control horn not affected;
middle panel: rat, EI (arrow)
decreased the EMG (bottom) and IUP (top);
bottom panel: human, EI (arrows)
subjectively toco (bottom) was decreasedj
and had no effect on FHR (top) or maternal
heart rate (not shown).
Note! decreased resting uterine smooth muscle
tone for several minutes after only 2 seconds
(RMS) of EI (B, solid lines in middle and bottom
panels) even without EI applied.
Karsdon et. al. Am J Obstet Gynecol. 2005; 193, 1986-1993
Results:
EI increased smooth muscle
relaxation (table):
1) EI decreased rabbit IUP.
2) EI, both directly and by
TVC, increased rat pup BI
by 1941% and 628%
respectively.
3) EI in women decreased
toco contraction frequency
or increased peak-to-peak
(P-P) interval time.
Mechanism: EI is thought to:
1) hyperpolarize the cell
membrane;
2) resulting in decreased
membrane depolarization;
3) thus decreased electrical
activity;
4) producing decreased smooth
muscle contractions or tone.
Category
Gestational
Age
mean±SD
N
Controls
mean±SD
N
EI
mean±SD
Rabbit Direct Uterine Pacemaker
(IUP )
30.3±1.6
(days)
14
33.0±15.0
(mmHg)
14
17.6±12.9*
(mmHg)
Rat Direct Uterine Pacemaker
(BI)
21.0±0.8
(days)
35
17.5±2.2
(minutes)
17
357.1±150.3*
(minutes)
Rat Vaginal Pacemaker
(BI)
21.6±1.3
(days)
19
17.2±8.3
(minutes)
36
125.2±43.9*
(minutes)
Human Vaginal Pacemaker
(P-P)
31.1±2.2
(weeks)
8
3.2±1.3 pre
3.2±1.3 post
(minutes)
8
3.8±1.4*
(minutes)
X
X
X
DECREASED TONE
Conclusions:
 Smooth muscle contractions/tone are the result of EMG activity
 Decreased EMG activity results in decreased smooth muscle contractions/tone
 Decreased vascular smooth muscle tone is associated with increased blood flow
 Electrical Inhibition (EI) decreases EMG activity
 EI is localized unlike pharmaceuticals and may hyperpolarize the cell membrane
 EI decreased (uterine) smooth muscle contractions/tone in animals and humans
 EI may have a use in decreasing human smooth muscle contractions/tone:
 uterine contractions of preterm births;
 neonatal pathologies e.g. persistent pulmonary hypertension
Contact: Dr. Jeffrey Karsdon, M.D.
Email: [email protected]